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Abstract

The present study assayed the antimutagenic potential of Salvia officinalis (sage) in the form of tea infusion, by the somatic mutation and recombination test (SMART) on Drosophila melanogaster. The use of herbal infusions is much common in the human diet, so the aim of the present study was to estimate the antimutagenic effects of the S. officinalis tea rather than essential oils. Methyl methanesulphonate (MMS) was used as the mutagen and positive control. Several types of treatment were performed: short acute treatment with sage infusion or MMS, longer (chronic) treatment with sage solution or MMS, and two combined treatments, i.e. short treatment with sage followed by a longer treatment with MMS and vice versa. Sage infusion used in our experiments showed a clear antimutagenic effect, reducing the frequency of mutations induced by MMS. The inhibition effect of sage tea is obtained and confirmed when pre- or post-treatments with mutagen were used. The results indicate that although sage in this regime decreases the number of mutation events, it is not efficient enough in case of the 2 h sage pre-treatment. Antioxidant activity, suppression of metabolic activation, could be mechanisms through which sage or some of its components act as desmutagen.

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... Th e areal parts (Salvia folium) are included in several European Pharmacopeias and the council of Europe lists the drug as a natural source for food fl avoring (Council of Europe, European Pharmacopeia, seventh ed., 2010). It has been used as an antidiabetic (Swanston-Flatt et al., 1991;Eidi and Eidi, 2009;Hamidpour et al., 2013), antioxidans (Nickavar et al., 2007;Yadav and Mukundan, 2011), anti-infl ammatory (Baricevic et al., 2001), antimicrobial (Khalil andLi, 2011), antiviral (Schnitzler et al., 2008;Smidling et al., 2008), gastroprotective and antimutagen (Patenković et al., 2009) agent. Also, it has been proven to be effective in cardiovascular and cancer diseases (Itani et al., 2008;Pedro et al., 2010;Keshavarz et al., 2011) and in the treatment of mental and nervous conditions (Baricevic and Bartol, 2000;Perry et al., 2003;Iuvone et al., 2006;Eidi et al., 2006;Khan et al., 2011). ...
... Th ese results provide the pharmacological base for medicinal use of S. offi cinalis in treatment of gut disorders, such as diarrhea and abdominal colic. Patenković et al. (2009) demonstrated potential antimutagenic eff ect of S. offi cinalis tea whose mode of action might be through suppression of metabolism by antioxidative action. On the basis of these fi ndings, the anticancerogen activity of S. offi cinalis was also investigated. ...
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Dalmatian sage (Salvia officinalis L.) represents one of the most significant medicinal autochthonous species in flora of eastern Adriatic coast and islands. It is evergreen outcrossing perennial subshrub with short woody stems that branch extensively and violet flowers. Apart from being native to Mediterranean karst of west Balkan and Apenine peninsula it is cultivated in numerous countries worldwide with Mediterranean and temperate continental climate. From the earliest times it has been used in traditional medicine in healing gingiva, mouth cavity and the sore throat, against bacterial and fungal infections, for wound treatment, memory enhancement, for treating common cold, against sweating, stomach inflammation, ulcer formation, etc. Its essential oil has also been used in preservation of food and as spice as it gives both specific aroma and promotes digestion of food. The essential oil is extremely complex mixture of different active ingredients; however, the thujones and camphor are the dominant compounds and are the parameter by which S. officinalis is distinguished from other Salvia species. The great variability of essential oil composition and yield has been detected depending on various factors such as genotype, environmental conditions, phonological stage, plant parts used for the extraction of essential oil and drying procedure. Molecular genetic analysis of S. officinalis is still limited and comprises the use of RAPD markers, AFLP and SSR markers in assessing mostly the genetic variability and structure of wild S. officinalis populations.
... Also this effect may be due to antioxidant activity and suppression of metabolic activation, which could be mechanisms through which sage or some of its components act as desmutagen. The antioxidant effect of S. officinalis was also recorded by Patenkovic et al, (2009) and Dizaye, (2010) (33,34). ...
... The ability of S. officinalis extracts to reduce the M.I value can be traced to its chemical constituents such as taninnes that have the ability to block cell cycle progression. The study of Patenkovic et al, (2009) and Grzegorczyk and Wyso kinska, (2008) explained the effect of different extracts of S. officinalis on M.I attributed to the antioxidant effects of terpenoids which enhanced the cell death (33,35). The reduction in the M.I revealed a mitodepressive effect of the extract on dividing bone marrow cells of mice (36). ...
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Introduction and objectives: Reports indicated that extract of salvia officinalis has antioxidant and antihistaminic activities and could alleviate nephrotoxicity induced by cisplatin. This study was undertaken to investigate the possible cytotoxic and cytogenic effects of aqueous extract of Salvia officinalis on different tumor cell lines. Methods: The cytotoxicity of Salvia officinalis extracts were evaluated on two tumor cell lines Rabdomyosarcoma (RD) and Murine mammary adenocarcinoma (AMN3), and one normal cell line, Murine fibroblast (L20B). The cytogenetic effects of the plant extract was studied after estimating the Cytotoxicity concentration 50% (CC50) value, on both tumor cell lines and human blood lymphocytes. Whereas 18 albino mice were used to study the in vivo cytogenic effects of Salvia officinalis after determining its Median Lethal dose (LD50). Results: The aqueous extract of S. officinalis has dose dependant cytotoxic effects on tumor cell lines. The results revealed that high significant cytotoxic effect was seen in highest concentrations on RD tumor cell line and AMN3 tumor cell with CC50 5400 μg/ml and 7810 μg/ml respectively. Salvia officinalis extracts induced a significant increase in L20B cell line proliferation. AMN3 tumor cell line was more sensitive to Cisplatin than RD tumor cell line. The cytogenetic effect of aqueous extracts of S. officinalis showed a significant decrease in mitotic index in all concentrations on both tumor cell lines. The plant extract caused a significant decrease in M.I of human blood lymphocyte at 48 hours. However their cytogenetic effect was less than that of Cyclophosphamide (CP). The LD50 of aqueous extracts of S. officinalis leaves is estimated to be 4361 mg/kg. Cytogenetic studies showed significant decrease in mitotic index in all treated mice. Conclusion: 1-Aqueous extracts of S. officinalis has antiproliferative effects on both RD and AMN3 cell lines. 2-Their cytotoxic activity was more efficacious than Cisplatin. 3-The cytogenic effects of the plant extract were less than that of Cyclophosphamide.
... Numerous biological activities of different extracts of Salvia and Ocimum species have been described, including antimicrobial, anti-inflammatory, antioxidative, antidiarrheal, blood-sugar lowering, immunomodulatory, a nervous system stimulatory, spasmolytic, and cholinergic binding [29][30][31][32][33][34][35][36][37][38][39][40]. Several reports also indicate antigenotoxic and chemopreventive activities of different extracts from Salvia and Ocimum species [41][42][43][44][45]. ...
... Although no genotoxicity of Thu was detected in SMART test [106], Kim et al. [109] reported co-mutagenic effect on aflatoxin B1-induced mutagenesis in S. typhimurium TA100. Besides our results, no antigenotoxic effect of Thu was reported, but there is evidence about antigenotoxicity of plant extracts containing high proportion of Thu [45,117]. ...
Chapter
Salvia and Ocimum are genera of the family Lamiaceae consisting of about 900 and 35 species, respectively. S. officinalis and O. basilicum are employed as folklore remedy for a wide spectrum of ailments in many traditional medicines, including ours. Furthermore, the latter is irreplaceable spice of many national cuisines. Numerous biological activities of different extracts of Salvia and Ocimum species have been described, including antimicrobial, anti-inflammatory, antioxidative, antidiarrheal, blood-sugar lowering, immunomodulatory, a nervous system stimulatory, spasmolytic, and cholinergic binding [29-40]. Several reports also indicate antigenotoxic and chemopreventive activities of different extracts from Salvia and Ocimum species [41-45]. In order to identify antimutagens with antioxidative properties, we modified our E. coli K12 assay for bioantimutagens. In repair proficient strain SY252 mutations are induced by t-butyl hydroperoxide (t-BOOH), a latent donor of ROS, which promotes oxidative damage of DNA [70]. Since DNA damage induced by t-BOOH cause both transitions and transversions of AT base pairs, it can be used to increase argE3 → Arg⁺ reversions. The mutT strain was constructed for the assay in order to evaluate protective capacity of antioxidants against formation of oxidatively damaged bases in the cell pool [57]. Due to deficiency in removing 8-oxo-G, mutT strains have high frequency of A:8-oxo-G mispairs and show increased level of spontaneous AT→CG transversions [71]. During validation of the test we determined that the frequency of argE3 → Arg⁺ reversions is significantly increased in IB106 strain [47]. Since MMR is additionally involved in the repair of mispairs between normal and oxidized bases [72], MMR deficient strains from the assay for bioantimutagens are also included. Protective effect of sage extracts against spontaneous and ethidium bromide (EtBr)-induced mutagenesis was monitored in E. coli K12 mutT and S. typhimurium TA98 strains, respectively [81]. The results showed that extracts of cultivated sage obtained at 500 bar (E1/5 and E2/5) exerted significant antimutagenic effect (Figure 1), indicating high molecular weight terpenes as active substances. The most effective extract E2/5, containing mainly rosmanol-9-ethyl ether (40%), was further investigated in order to elucidate the molecular mechanism of antimutagenicity. Different experimental procedures were applied: A – co-incubation of mutagen, extract and S9 fraction, followed by addition of bacteria and plating; B – pre-incubation of mutagen and S9, followed by addition of the extract, incubation, and final addition of bacteria and plating; C- pre-incubation of mutagen, S9 and bacteria, followed by removal of mutagen and S9, addition of the extract, and plating. The strongest inhibition was obtained when the mutagen and E2/5 were pre-incubated with S9 (procedure A), indicating that the main antimutagenic mechanism was inhibition of metabolic activation of EtBr. Extract E2/5 also moderately reduced spontaneous mutations (37%) in mutT strain.
... This effect may be due to antioxidant activity and suppression of metabolic activation, which could be mechanisms through which sage or some of its components act as desmutagen. The antioxidant effect of S. officinalis was recorded by Patenkovic et al. (2009) andDizaye (2010). ...
... The ability of S. officinalis extracts to reduce the mitotic index (M.I) value can be traced to its chemical constituents such as taninnes that have the ability to block cell cycle progression Al-Barazanjy et al. (2013). The study of Patenkovic et al. (2009) and Grzegorczyk and Wysokinska (2008) explained the effect of different extracts of S. officinalis on M.I attributed to the antioxidant effects of terpenoids, which enhanced the cell death. In bone marrow cells of mice, reduction in the M.I exposed a mitodepressive ability of the extract of Sage on division Modallal et al. (2008). ...
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Experimental studies on the toxicity of the sage are scarce despite its use in traditional medicine. So, this research is conducted to evaluate the toxicity of sage extract during the gestation period in female rats. 30 virgin female pregnant rats were divided into control and treated groups, 15 rats in each group. The treated group was received 500mg/kg rat of sage diluted in saline, from the 5th to 20thday of pregnancy. The control group received saline water at the same time. The gravid uteri of the pregnant dams were removed and its fetuses were extracted, then the fetal liver and kidney were stained with haematoxylin and eosin (H&E). The light microscopic examination of the fetal liver showed several hemorrhagic sites, rupture of endothelial cells lining the central vein with dilatation in the central vein and accumulation of the red blood cells and macrophages. Also, an increased in the number of erythroblasts and megakaryocytes are observed. Examination of the fetal kidney maternally treated with sage indicated that glomeruli appeared shrunken, swollen with wide, narrow capsular spaces respectively. The convoluted tubules show some abnormal changes in its histological organization; Nuclei of its epithelial cells are pykcnotic with condensation in chromatin material. In addition, nuclei and cytoplasm of cells, which form the proximal and distal tubules show degeneration and necrosis on it. Saliva officinal is should be considered as a drug and handled with precaution. Care must be taken to control the amount of plant extract taken by man
... The plants of Salvia spp inhibit cell division of tumor cells and have antigenotoxic and -microbial effects (Goze et al., 2009;Kaileh et al., 2007;Loizzo et al., 2009;Patenkovic et al., 2009;Sivropoulou et al., 1997;Vujosevic & Blagojevic, 2004). On the other hand, some reports have emphasized the adverse effects of Stachys plants (Al-Hamood et al., 1998;Hu et al., 2009;Perfumi et al., 1991) and for some essential oils that developed from unintended concequences resulting from use of the plants (Buyukleyla & Rencuzogullari, 2009;Chiang et al., 1997;Gurley et al., 2010;Háznagy-Radnai et al., 2008;Kayraldiz et al., 2010;Qu et al., 1992;Rencuzogullari et al., 2009). ...
... The antimutagenic effects of Salvia officinalis were tested in the mammalian system and it was reported that this plant extract decreased the chromosomal abnormalities (Loizzo et al., 2009;Vujosevic & Blagojevic, 2004). S. officinalis also had an antimutagenic effect in somatic mutation and the recombination test (Patenkovic et al., 2009). In light of these reports and based upon our results, we conclude that Sf, if used at higher concentrations, might have some antigenotoxic effect in an in vivo system. ...
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Abstract The aim of this study was to investigate the genotoxic and antigenotoxic effects of Salvia fruticosa (Sf) leaf extract with the absence and presence of S9 mix using sister chromatid exchange (SCE), chromosome aberration (CA) and micronucleus (MN) formation test systems in human peripheral blood lymphocytes (HPBLs) that were treated with 1.5-, 3.0- and 6.0-µL/mL concentrations for 24- and 48-hour treatment periods. The cytotoxicity of Sf leaf extract was also investigated by calculating the mitotic index (MI), proliferation index (PI) and nuclear division index (NDI). In the absence of S9 mix, Sf leaf extract alone increased SCE frequency at the 48-hour treatment period; however, it induced the CA and MN at all concentrations and at all treatment periods. Sf plus MMC (mitomycin C) synergically induced SCE and CA, except the highest concentration of Sf leaf extract and MMC on induction of SCE. In addition, Sf leaf extract induced the effect of MMC on MN frequency for 24 hours, but it significantly decreased the effect of MMC on MN frequency for the 48-hour treatment period. Sf leaf extract showed a cytotoxic effect by decreasing the MI; however, it did not decrease the PI and NDI. In the presence of S9 mix, Sf leaf extract did not increase the SCE, when compared to solvent control, whereas it reduced the effect of cyclophosphamide (Cyp). Sf leaf extract induced the CA and MN, but could not increase the effect of Cyp on CA and MN formation. Sf leaf extract had no cytotoxic effect; however, it induced the cytotoxicity of Cyp.
... This effect may be due to antioxidant activity and suppression of metabolic activation, which could be mechanisms through which sage or some of its components act as desmutagen. The antioxidant effect of S. officinalis was recorded by Patenkovic et al. (2009) andDizaye (2010). ...
... The ability of S. officinalis extracts to reduce the mitotic index (M.I) value can be traced to its chemical constituents such as taninnes that have the ability to block cell cycle progression Al-Barazanjy et al. (2013). The study of Patenkovic et al. (2009) and Grzegorczyk and Wysokinska (2008) explained the effect of different extracts of S. officinalis on M.I attributed to the antioxidant effects of terpenoids, which enhanced the cell death. In bone marrow cells of mice, reduction in the M.I exposed a mitodepressive ability of the extract of Sage on division Modallal et al. (2008). ...
Article
Full-text available
Experimental studies on the toxicity of the sage are scarce despite its use in traditional medicine. So, this research is conducted to evaluate the toxicity of sage extract during the gestation period in female rats. 30 virgin female pregnant rats were divided into control and treated groups, 15 rats in each group. The treated group was received 500mg/kg rat of sage diluted in saline, from the 5th to 20thday of pregnancy. The control group received saline water at the same time. The gravid uteri of the pregnant dams were removed and its fetuses were extracted, then the fetal liver and kidney were stained with haematoxylin and eosin (H&E). The light microscopic examination of the fetal liver showed several hemorrhagic sites, rupture of endothelial cells lining the central vein with dilatation in the central vein and accumulation of the red blood cells and macrophages. Also, an increased in the number of erythroblasts and megakaryocytes are observed. Examination of the fetal kidney maternally treated with sage indicated that glomeruli appeared shrunken, swollen with wide, narrow capsular spaces respectively. The convoluted tubules show some abnormal changes in its histological organization; Nuclei of its epithelial cells are pykcnotic with condensation in chromatin material. In addition, nuclei and cytoplasm of cells, which form the proximal and distal tubules show degeneration and necrosis on it. Saliva officinal is should be considered as a drug and handled with precaution. Care must be taken to control the amount of plant extract taken by man.
... Th e pharmacological properties of S. offi cinalis extract, which are mostly described as antioxidants, might explain the way in which it protects the tissues and bone marrow chromosomes against CYP-induced genotoxicity and oxidative stress. It was reported that essential oil of S. offi cinalis L. and S. offi cinalis (sage) in the form of tea infusion did not show any mutagenic eff ect and showed antimutagenic eff ect against UV-induced mutations in Escherichia coli and Saccharomyces cerevisiae in the Salmonella/microsome mutagenicity assay Ames test (22) and in the wing spot test of Drosophila melanogaster, respectively (63). Th e latter authors concluded that antioxidant activity and suppression of metabolic activation could be mechanisms through which sage or some of its components act as desmutagens (63). ...
... It was reported that essential oil of S. offi cinalis L. and S. offi cinalis (sage) in the form of tea infusion did not show any mutagenic eff ect and showed antimutagenic eff ect against UV-induced mutations in Escherichia coli and Saccharomyces cerevisiae in the Salmonella/microsome mutagenicity assay Ames test (22) and in the wing spot test of Drosophila melanogaster, respectively (63). Th e latter authors concluded that antioxidant activity and suppression of metabolic activation could be mechanisms through which sage or some of its components act as desmutagens (63). In our study, the inhibition of micronucleus formation by the extract suggests that the antimutagenic potential of the extract is mostly probably due to antioxidant and anticarcinogenic activity related to the high antioxidant capacity of the extract. ...
Article
Medicinal plants, especially rich in polyphenolic compounds, have been suggested to be chemopreventive on account of antioxidative properties. Salvia officinalis L., an aromatic and medicinal plant, is widely used in folk medicine and is well known for its antioxidant properties. Therefore, the present study was designed to investigate the antioxidative, possible genotoxic, and antigenotoxic potency of S. officinalis extract against cyclophosphamide (CYP)-induced oxidative stress and genotoxicity in Wistar albino rats. Animals were orally dosed with S. officinalis extract (50, 100, and 150 mg/kg body weight) for 7 days before the administration of a single intraperitoneal dose of CYP (40 mg/kg body weight). The biochemical and cytogenetic determinations were carried out 24 h aft er CYP injection. The activities of malondialdehyde, superoxide dismutase, and catalase were determined in liver, kidney, and heart tissues. The frequency of micronucleated polychromatic erythrocytes (MNPCEs) and the ratio of polychromatic erythrocytes to normochromatic erythrocytes (PCE/NCE) were also evaluated. Additionally, the antioxidant capacity of the extract was analyzed. The micronucleus assay revealed that all doses of the extract tested presented no genotoxic activity; in addition, the 2 highest doses reduced the MNPCEs and increased the PCE/NCE ratio in the bone marrow and restored the oxidative stress markers in CYP-treated rats. In correlation with these findings, S. officinalis extract exhibited high antioxidant capacity. The results of the present study suggest that the methanolic extract of S. officinalis has a protective effect against CYP-induced oxidative stress and genotoxicity through its antioxidant property.
... Also this effect may be due to antioxidant activity and suppression of metabolic activation, which could be mechanisms through which sage or some of its components act as desmutagen. The antioxidant effect of S. officinalis was also recorded by Patenkovic et al, (2009) ...
... Many essential oils are classified as "generally regarded as safe" (GRAS) by the United States Food and Drug Administration (FDA), and so are potential targets for developing natural antimicrobial products owing to their safety with eukaryotic systems [29,30]. Essential oils are known to induce a wide range of biological effects through their antibacterial, antioxidant, antifungal, and antimutagenic activities [2,18,20,25]. Several studies have demonstrated the antiviral activities and antiviral mechanisms of various types of essential oils and individual compounds against herpes simplex virus type 1 (HSV-1), HSV-2, influenza A/PR/8 virus, infectious bronchitis virus (IBV), and SARS-CoV in vitro and in vivo [4,11,13,15,26]. ...
Article
Essential oils are increasingly of interest for use as novel drugs acting as antimicrobial and antiviral agents. In the present study, we report the in vitro antiviral activities of 29 essential oils, extracted from Chinese indigenous aromatic plants, against the tobacco mosaic virus (TMV). Of these essential oils, those oils from ginger, lemon, tea tree, tangerine peel, artemisia, and lemongrass effected a more than 50% inhibition of TMV at 100 microng/ml. In addition, the mode of antiviral action of the active essential oils was also determined. Essential oils isolated from artemisia and lemongrass possessed potent inactivation and curative effects in vivo and had a directly passivating effect on TMV infection in a dose-dependent manner. However, all other active essential oils exhibited a moderate protective effect in vivo. The chemical constitutions of the essential oils from ginger, lemon, tea tree, tangerine peel, artemisia, and lemongrass were identified by gas chromatography and gas chromatography-mass spectrometry. The major components of these essential oils were alpha-zingiberene (35.21%), limonene (76.25%), terpinen-4-ol (41.20%), limonene (80.95%), 1,8-cineole (27.45%), and terpinolene (10.67%). The curative effects of 10 individual compounds from the active essential oils on TMV infection were also examined in vivo. The compounds from citronellal, limonene, 1,8-cineole, and alpha-zingiberene effected a more than 40% inhibition rate for TMV infection, and the other compounds demonstrated moderate activities at 320 microng/ml in vivo. There results indicate that the essential oils isolated from artemisia and lemongrass, and the individual compound citronellal, have the potential to be used as an effective alternative for the treatment of tobacco plants infected with TMV under greenhouse conditions.
... The first study of the antigenotoxicity by the wings SMART assay of D. melanogaster was published in 1989 by Negishi et al. (1989). Since then, the method was used in several studies of the antimutagenicity (Graf et al., 1998; Patenkovic et al., 2009). Thus in this work, the antimutagenic activity of argan oil in Drosophila was recorded. ...
Article
Argan oil is receiving increasing attention due to its potential health benefits in the prevention of cardiovascular and cancer risk, but no information to date is available about its genotoxic or antigenotoxic effect. The genotoxicity and the antigenotoxicity of commercial argan oil and its unsaponifiable fraction (UF) against Drosophila melanogaster was evaluated using wing spots enumeration. Results showed that the argan oil (at 20% dosage) and the UF (at 0.112 g/l) were not genotoxic. Results on the effects of argan oil and UF on the mutagenic properties of methyl methanesulfonate (MMS) and ethyl carbamate (urethane) showed an inhibition rate of 54 and 43% against MMS and urethane, respectively, by argan oil and 56 and 75% against urethane and MMS, respectively, by UF. The result of the present study suggests that argan oil prevent mutations induced by urethane and MMS in D. melanogaster, as a consequence consumption of argan oil can prevent human DNA lesion induced by some environmental mutagens.
... Although the neurotoxic effect of Thu in mammals is well established (Höld et al., 2000), reported data indicate that Thu is not genotoxic (http://ntp-apps.niehs.nih.gov/). Moreover, essential oils containing Thu have been widely used in traditional medicine and there are indications of their antimutagenic properties (Minnunni et al., 1992;Vuković-Gačić et al., 2006a;Patenković et al., 2009; www.ema.europa.eu/pdfs/vet/mrls/060299en. pdf). ...
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The aim of this work was to investigate the antimutagenic potential of monoterpenes from sage and basil in Escherichia coli. The mutagenic potential of monoterpenes was pre-screened with Salmonella/microsome reversion assay in strain TA100 and no mutagenic effect was detected. The antimutagenic potential against UV- 4NQO- and t-BOOH-induced mutagenesis was evaluated in E. coli K12 and E. coli WP2 by reversion assays. The obtained results indicate that camphor and thujone reduce UV- and 4NQO-induced mutations; myrcene reduces t-BOOH-induced mutations, while eucalyptol and linalool reduce mutagenicity by all tested mutagens. Considering evolutionary conservation of DNA repair and antioxidative protection, the obtained results indicate that further antigenotoxicity studies should be undertaken in eukaryotes.
... É nativa da região mediterrânea da Europa e suas partes aéreas são popularmente utilizadas para o tratamento da dispepsia, ansiedade, dos sintomas do climatério, como anti-inflamatória e no controle do diabetes (Walch et al., 2011). Alguns estudos têm mostrado que extratos de S. offinalis podem reduzir significativamente os níveis de glicose em ratos diabéticos (Eidi et al., 2005), potencializar a capacidade antioxidante do fígado (Lima, 2005) e apresentarem in vitro, efeitos antimutagênico (Patenkovic et al., 2009) e antiangiogênico (Keshavarz et al., 2010). A atividade gastroprotetora do extrato hidroalcoólico S. offinalis foi observada por Mayer et al. (2009) e as atividades farmacológicas, provavelmente estão relacionadas com a presença de polifenóis como carnosol (Topçu, 2006), apigenina, hispidulina, ácidos caféico, rosmarínico e ursólico (Imanshahidi et al., 2006). ...
Article
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As úlceras pépticas são decorrentes de um desequilíbrio entre os agentes agressores endógenos, exógenos e agentes protetores. Neste estudo avaliou-se a atividade antiulcerogênica in vivo para o extrato aquoso de Salviaofficinalis (EAS). Após os tratamentos (n = 6; v.o) com o controle (C) água; pantoprazol (30 mg/kg) e EAS (100, 250 e 400 mg/kg, respectivamente) os ratos receberam uma solução de HCl 0,3 M em etanol 60% (v.o) e realizaram-se avaliações morfológicas dos estômagos por meio de uma tabela de escores de lesão (ANOVA; one way e Tukey). EAS (400 mg/kg) apresentou atividade antiulcerogênica (31,47%) semelhante ao pantoprazol (33,83%) em comparação (p<0,0001) com o grupo C. A análise fitoquímica por cromatografia líquida de alta eficiência revelou uma elevada concentração de ácido rosmarínico (3,53%) para EAS. Os flavonoides (0,25%) e os fenóis totais (309,0 EAG) foram quantificados por espectrofotometria de UV/Vis. EAS e ácido rosmarínico apresentaram elevadas atividades antioxidantes por DPPH (Concentração Efetiva 50%-CE50 9,2 e 0,7 mg/mL, respectivamente) justificando pelo menos em parte, o efeito antiulcerogênico do extrato.
... Salvia extract can significantly decrease the DNA damage induced by flavomycin in a linear, dosedependent manner in partridges (Yurtseven et al., 2008). S. officinalis leaves possesssome therapeutic effects due to the presence of biochemicals like tannin, triterpenoids, flavonoids, estrogenic substances, saponins, and volatile oil, together with vitamins C and A (Patenkovic et al., 2009). ...
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Use of natural plant extracts to prevent the damage potency of various mutagens is on the rise. The aims of our study were: i) to evaluate the biological activity of Salvia officinalis (sage) water extract and its ability to reduce the zeocin-induced cytotoxic/genotoxic effects in Hordeum vulgare (barley) and human lymphocytes, ii) to obtain information about the susceptibility of plant chromosomes on the basis of " aberration hot spots " (AHS) under various experimental conditions of treatment. Sage extract had no or low cytotoxic effect and its clastogenic effects were clearly dependent on the concentration and test-systems. Lymphocytes were more susceptible to sage extract than barley. Sage extract applied in a higher but low-toxic concentration showed well expressed protective potential against zeocin. It decreased the chromosome aberrations and micronuclei induced by zeocin in both test-systems. The protective effect was manifested irrespective of the experimental design and test-systems. All AHS were found to be within heterochromatin-containing or terminal segments when barley meristems were treated with the radiomimetic. AHS were reduced and no longer located in heterochromatin-rich regions after sage treatment following different experimental designs. Our results might be useful in future health research programs and prophylactic therapy based on plant extracts.
... Sage may also inhibit pro-oxidant-induced lipid peroxidation in rat brain and liver homogenates (Oboh and Henle, 2009). Further in vitro models showed Salvia as possibly being antiangiogenic, antimutagenic, antidiabetic, and gastroprotective (Lima et al., 2006; Mayer et al., 2009; Patenkovic et al., 2009; Keshavarz et al., 2010). Although the underlying mechanisms of action are unknown, polyphenols such as carnosol, carnosic acid, rosmanol, apigenin, hispidulin, caffeic acid, and ursolic acid have been discussed as active compounds for these pharmacological effects (Imanshahidi and Hosseinzadeh, 2006). ...
Article
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Sage (Salvia officinalis L.) is used as an herbal medicinal product, with the most typical form of application as infusion with boiling water (sage tea). The well-established traditional uses include symptomatic treatment of mild dyspeptic complaints, the treatment of inflammations in the mouth and the throat, and relief of excessive sweating and relief of minor skin inflammations. In this study, sage teas prepared from commercially available products were chemically analyzed for polyphenolic content using liquid chromatography, for antioxidant potential using the oxygen radical absorbance capacity method, and for the Folin-Ciocalteu (FC) index. The sage teas showed a high variation for all parameters studied (up to 20-fold differences for rosmarinic acid). Univariate and multivariate analyses showed that the antioxidant potential, which varied between 0.4 and 1.8 mmol trolox equivalents/100 mL, was highly dependent on rosmarinic acid and its derivatives. The FC index also showed a high correlation to these polyphenols, and could therefore be used as a screening parameter for sage tea quality. The considerable differences in polyphenolic composition and antioxidant capacity between the brands lead to a demand for quality standardization, especially if these sage teas are to be used for therapeutic purposes. Further research also appears to be necessary to characterize the dose-benefit relationship, as sage may also contain a constituent (thujone) with potentially adverse effects.
... As in our study, in many studies in the literature, the effects of the antigenotoxic and antioxidative effects of various plant extracts having medical value and also used in the alternative medicine have been investigated in Drosophila by various test techniques, especially SMART (de Rezende et al. 2009;Patenkovic et al. 2009;Demir et al. 2013). As a result of our study, statistically, significant increases in lifespan were determined depending on the increasing white tea concentration. ...
... Furthermore, sage inhibited pro-oxidant-induced lipid peroxidation in rat brain and liver homogenates (Oboh and Henle, 2009). Additional studies suggested sage as an anti-diabetic (Lima et al., 2006), gastroprotective (Mayer et al., 2009), anti-mutagenic (Patenkovic et al., 2009), and anti-angiogenic agent (Keshavarz et al., 2011). In the literature, antimicrobial and antioxidant properties of sage have also been well described (Bozinet al., 2007;Grzegorczyk et al., 2007;Delamare et al., 2007). ...
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Herbal tea is commonly consumed beverage, brewed from the leaves, flowers, seeds, fruits, stems or roots of plant species, which has been widely used for health care and disease prevention for centuries. With the increase in consumption of herbal tea, attention has been paid to their possible effects on human health and the bioactive compounds accounted for these health-promoting properties. In this chapter, medicinal herbs namely linden (Tilia cordata), peppermint (Mentha piperita), rosemary (Rosmarinus officinalis), sage (Salvia officinalis) and thyme (Thymus vulgaris), which are often consumed as tea, were investigated in terms of their health-promoting properties and related bioactive constituents.
... Dried leaves are commonly used as a culinary spice for flavouring and seasoning. We studied the antimutagenic potential of S. officinalis by means of the somatic mutation and recombination test on D. melanogaster (Patenković et al. 2009). Methyl methanesulphonate was used as the mutagen, and different types of treatment were performed: short acute treatment with sage infusion or MMS, longer (chronic) treatment with sage solution or MMS and two combined treatments, i.e., short treatment with sage followed by longer treatment with MMS and vice versa. ...
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To gain more information on biological effects of plants, particularly herbs used in human medicine and diet, in vitro and in vivo methods have been developed to predict their genotoxicity and/ or antigenotoxicity in various test systems. The sex-linked recessive lethal (SLRL) and somatic mutations and recombination (SMART) tests are in vivo assays on D. melanogaster that have been used to test both mutagenic and antigenotoxic effects of extracts from numerous plant species used worldwide. The similarity of metabolic pathways between Drosophila and mammals and the ability to activate promutagens make the results of these tests widely applicable. Besides, Drosophila presents significant orthology with human genes that control cancers, which makes the assays on Drosophila reliable and informative for extrapolations onto humans.
... The most of the mutations that occur in natural populations are thought to be the result of spontaneous processes. However, induced mutagenesis may be the cause of a minute part of the genetic variability (Friedburg et al., 2006; Patenković et al., 2009 Patenković et al., , 2013). When populations are limited in size, chance factors may lead to random changes in allelic frequencies. ...
... Literature data about mutagenicity/genotoxicity of Thu are very limited: Kim et al. (1992) monitored its effect against mutagenesis induced by aflatoxin B 1 in S. typhimurium TA100 and interpreted their results as co-mutagenic effects of Thu. On the contrary, as we mentioned above no genotoxicity of Thu was detected by Pavlidou et al. (2004) and some literature data even indicated antimutagenic properties of essential oils containing Thu Minnunni et al., 1992;Patenković et al., 2009;Vuković -Gačić et al., 2006a). ...
Article
The aim of this work was to examine the antigenotoxic potential of plant monoterpenes: camphor, eucalyptol and thujone in prokaryotic and eukaryotic cells and to elucidate their effect on DNA repair. We compared the effect of monoterpenes on spontaneous, UV- and 4NQO-induced mutagenesis in Escherichia coli K12 repair proficient, and MMR and NER deficient strains. Positive controls tannic acid and vanillin were included in bacterial tests. We also examined protective effect of monoterpenes against 4NQO-induced genotoxicity in Vero cell line by alkaline comet assay. The results obtained in repair proficient strain indicated antimutagenic potential of monoterpenes against UV- and 4NQO-induced mutagenesis, which was diminished with NER deficiency. Camphor and eucalyptol maintained UV-induced SOS response longer than in controls, while thujone decreased SOS response and reduced general protein synthesis and the growth rate. The three monoterpenes increased spontaneous and UV-induced recombination in recA730 and camphor additionally in recA(+) cells. Incubation of 4NQO-pretreated Vero cells with monoterpenes resulted in significant reduction of tail moment. However, higher concentrations of monoterpenes induced DNA strand breaks. Obtained results indicate that by making a small amount of DNA lesions camphor, eucalyptol and thujone can stimulate error-free DNA repair processes and act as bioantimutagens.
... This assay can detect a wide range of mutational events such as point mutations, deletions, certain types of chromosome aberrations (non-disjunction) and mitotic recombination [12]. It should be noted that this in vivo system assay has proved to be versatile and suitable for mutagenic and antimutagenic studies of different medicinal plant extracts [13][14][15], or their isolated bioactive components [16, 17]. ...
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Buddleja globosa is an endemic shrub species from South America with recognized wound healing, analgesic, anti-inflammatory and antioxidant properties; however, there are not studies about their mutagenicity/antimutagenicity potential. To this end, we used the wing-spot test in Drosophila melanogaster to assess mutagenic and antimutagenic activities of B. globosa. Treatments with different non-toxic concentrations of aqueous extracts from B. globosa leaves did not induce a significant increase in the frequency of any class of mutant spot formation on the wing blades of adult flies. Combined treatments with the mutagenic agent ethyl methane sulphonate (EMS) and leaf extracts showed a relevant reduction of single, large and total mutant spots in somatic wing cells in comparison to those induced by the EMS alone. The results indicate that aqueous extracts of B. globosa show desmutagenic effects in an in vivo model on D. melanogaster. Verbascoside and luteolin are the main bioactive components isolated from B. globosa leaf extracts and these kind of polyphenols could be related with their antimutagenicity. This study is the first in assessing the mutagenic and antimutagenic potential of B. globosa.
... In addition, researchers found that hybridization yielded positive relations with many economic characteristics of the plant. Some Salvia species have been reported to have genotoxic, antigenotoxic, and anti-carcinogenic effects (Karakaya and Kavas, 1999;Vujosevik and Blagojevic, 2004;Loizzo et al. 2007;Patenkovic et al. 2009;Russo et al. 2013;Sevindik and Rencuzogullari, 2014;Kizilet et al. 2019). Because of their main components, species having anti-carcinogenic effects Salvia 5 show cytotoxic or cytostatic effect by causing cell death (Beladjila et al. 2018). ...
Chapter
Salvia spp. are a genus of herbaceous plants characterized by woody stems and lanceolate leaves grouped in spikes of bluish-purple leaves with wavy margins. The salvia species most commonly used as additives in animal diets are: Salvia lavandulifolia, Salvia officinalis and Salvia hispanica. One species of particular interest for livestock nutrition is Salvia hispanica, for which favorable results for average daily gain have been observed at dietary inclusion rates of 1-40% in species as varied as rabbits, goats, chickens, lambs, cattle, and quail. In rabbits, Salvia hispanica is added to diets with the goal of improving vascular function in hypercholesterolemic conditions. Common commercial rabbit diets can raise cholesterol levels, while Salvia hispanica increases levels of triacylglycerol and alpha linoleic acids, the latter of which are involved in improved vascular function. Addition of Salvia hispanica additionally alters fat partitioning and storage in rabbits, improving meat quality. Supplementation of diets with Salvia hispanica contributes to improved efficiency and improved economic gains for small producers, thereby improving the sustainability of rabbit production. The use of natural herbs such as Salvia spp. also allows for improved productivity in a manner perceived by consumers and regulatory agencies to be more “natural” than synthetic growth promoters. The objective of this review is therefore to demonstrate the benefits of the addition of Salvia spp. to commercial rabbit diets.
... In addition, researchers found that hybridization yielded positive relations with many economic characteristics of the plant. Some Salvia species have been reported to have genotoxic, antigenotoxic, and anti-carcinogenic effects (Karakaya and Kavas, 1999;Vujosevik and Blagojevic, 2004;Loizzo et al. 2007;Patenkovic et al. 2009;Russo et al. 2013;Sevindik and Rencuzogullari, 2014;Kizilet et al. 2019). Because of their main components, species having anti-carcinogenic effects Salvia 5 show cytotoxic or cytostatic effect by causing cell death (Beladjila et al. 2018). ...
Chapter
Salvia divinorum is a plant of the genus Salvia that belongs to the family of mint Lamiaceae which grows mainly in Oaxaca - Mexico in very humid environments and rich soils. S. divinorum is usually known as “Ska Pastora” or “Ska Maria Pastora”, having more common names among the youth community as “magic mint”, “Diviner’s Sage”, “Sally D” or “Purple Sticky”. Until the mid-60s, knowledge of this genus/family was restricted to an indigenous group located northeast of Oaxaca in Mexico, the Mazatecs, who used it for several centuries during their divine ceremonies, healing processes and in the training of healers. Some studies carried out with S. divinorum and its bioactive compound (salvinorin A), showed that it has effects with potential interest for human therapy, such as in the treatment of drug dependence, pain, neurological, gastrointestinal diseases and as anti-inflammatory drug. However, in the last years it has been consumed as a recreational drug of abuse due to its psychoactive proprieties. Both S. divinorum and salvinorin A have become controlled drugs in several countries, but they are not listed in the Schedules of the United Nations Drug Conventions. This chapter will aim to perform a critical review about Salvia divinorum and its components, modes of consumption, effects, interactions, therapeutic uses, their determination in biological specimens and laboratory difficulties; other toxicological aspects will be discussed as well. Keywords: Salvia divinorum, salvinorin A, effects, therapeutic uses, toxicological aspects
... It has a very long history of effective uses against bacterial and viral infections (Jakovljević et al., 2019). It can also be used for its hypotensive properties, mental actions, antispasmodic activity (Eidi, Eidi, & Bahar, 2006) and antimutagenic potential (Patenkovic, Stamenkovic-Radak, Banjanac, & Andjelkovic, 2009). ...
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Alterations in testicular apoptosis, cell cycle progression and proliferation rate in dietary‐induced obese male rats and role of oral administration of marjoram (0.16 ml/kg BW) and sage (0.05 ml/kg BW) oils were evaluated. Results showed increased body weight, serum leptin, testicular lipid peroxidation, protein oxidation and nitric oxide, with reduction in serum testosterone, sperm count and endogenous enzymatic and non‐enzymatic antioxidants in testis of the obese rats. Flow cytometry results revealed increased number of annexin‐V (+ve) cells with activation of apoptotic proteins (Bax, caspase‐3) and reduction of anti‐apoptotic Bcl‐2. Cell cycle arrest at phases S and G2/M with decline in expression of Bcl‐2 and germ cell proliferation marker ki‐67 was also validated, indicating lowered spermatogenesis in the obese rats. Supplementation of marjoram or sage oils displayed normalized body weight, sperm count, germ cells apoptosis and proliferation, suggesting the two oils as a new therapeutic approach against obesity promoted male infertility. Practical applications Obese men have a greater chance of fertility problems compared to those with normal weight. Obesity‐associated oxidative stress and free radicals production have shown to adversely affect sperm quality with activation of pro‐apoptotic pathways, allowing germ cell death. Marjoram and sage essential oils are now being widely studied due to their antioxidant and radical scavenging properties. Our findings indicated effectiveness of the two oils for combating body weight gain, testicular oxidative stress, and apoptosis, which seemed to aid in increasing sperm count. The outcomes of this study may help scientists to formulate novel medications for improving fertility problems in men.
... In addition, researchers found that hybridization yielded positive relations with many economic characteristics of the plant. Some Salvia species have been reported to have genotoxic, antigenotoxic, and anti-carcinogenic effects (Karakaya and Kavas, 1999;Vujosevik and Blagojevic, 2004;Loizzo et al. 2007;Patenkovic et al. 2009;Russo et al. 2013;Sevindik and Rencuzogullari, 2014;Kizilet et al. 2019). Because of their main components, species having anti-carcinogenic effects Salvia 5 show cytotoxic or cytostatic effect by causing cell death (Beladjila et al. 2018). ...
Book
Salvia spp. are a genus of herbaceous plants characterized by woody stems and lanceolate leaves grouped in spikes of bluish-purple leaves with wavy margins. The salvia species most commonly used as additives in animal diets are: Salvia lavandulifolia, Salvia officinalis and Salvia hispanica. One species of particular interest for livestock nutrition is Salvia hispanica, for which favorable results for average daily gain have been observed at dietary inclusion rates of 1-40% in species as varied as rabbits, goats, chickens, lambs, cattle, and quail. In rabbits, Salvia hispanica isadded to diets with the goal of improving vascular function in hypercholesterolemic conditions. Common commercial rabbit diets can raise cholesterol levels, while Salvia hispanica increases levels of triacylglycerol and alpha linoleic acids, the latter of which are involved in improved vascular function. Addition of Salvia hispanica additionally alters fat partitioning and storage in rabbits, improving meat quality. Supplementation of diets with Salvia hispanica contributes to improved efficiency and improved economic gains for small producers, thereby improving the sustainability of rabbit production. The use of natural herbs such as Salvia spp. also allows for improved productivity in a manner perceived by consumers and regulatory agencies to be more “natural” than synthetic growth promoters. The objective of this review is therefore to demonstrate the benefits of the addition of Salvia spp. to commercial rabbit diets.
... For example, S. officinalis essential oil and its monoterpenes (camphor, 1, 8-cineole, thujone, and limonene) exerted their safety and antimutagenic activity against ultraviolet irradiation in bacteria Escherichia coli and yeast Saccharomyces cerevisiae (Vukovic-Gacic et al. 2006). Likewise, water extract of S. officinalis demonstrated it safety and antimutagenic activity induced by methyl methanesulphonate in the wing spot test of Drosophila melanogaster (Patenkovic et al. 2009). Further, exposing rats to 80% methanol extract of aerial part of S. officinalis (50, 100, and 150 mg/kg, orally, for 7 days) indicating its safety and antigenotoxicity against cyclophosphamide in rat bone marrow cells (Alkan et al. 2012). ...
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The present research designed to assess the protective role of Salvia officinalis essential oil (SO) against carbon tetrachloride (CCl4)-induced liver and kidney damage in mice. This is evidenced by estimation of antiradical scavenging activity of SO using DPPH assay, biochemical markers, histological investigation of liver and kidney sections, and comet assay. Mice were given CCl4 (1.2 mL/kg for 24 h or 0.8 mL/kg for 2 weeks, 3 times/week) and with or without SO (0.1, 0.2, and 0.4 mL/kg, for 2 week, 5 times/week). The findings demonstrated that both acute and subacute treatment with CCl4 alone had adverse side effects on liver and kidney of mice. These effects were evidenced by a significant increase in serum hepatic enzymes (ALT, AST, ALP, LDH, and G-GT), bilirubin, and renal function markers (blood urea, creatinine). Toxic effect of CCl4 was accompanied by a decline in the serum total protein, albumin, globulin, and prothrombin (%). CCl4 induced oxidative stress as evidenced by increasing serum lipid peroxidation (LPO) along with decreasing serum total glutathione S transferase (GST). A remarkable increase in hepatic DNA strand breakages and histopathological distortion in liver and kidney specimens were observed in CCl4-intoxicated groups. Ultrastructurally, hepatocytes exhibited irregular nuclei, vacuolated cytoplasm, and distorted microorganelles. Essential oil form S. officinalis possessed antiradical scavenging (EC50 = 4602 μg/mL) lower than ascorbic acid (EC50 = 5.9 μg/mL). This oil was effectively exhibited hepato-nephroprotective activity especially at its higher concentrations in co-treated groups (SO plus CCl4). The activity of SO was associated with lowering the liver enzymes, bilirubin, urea, and creatinine, along with increasing total protein, albumin, globulin, and prothrombin. The increase in GST content and the decrease in LPO and DNA breakage levels, alongside repairing the histo-architectural distortions further confirmed the protective activity of SO. SO is a potential candidate for counteracting hepato/renal injury associating CCl4. This effect may occur via antioxidant defense mechanism which in part related to the complexity of its chemical constituents.
... Several in vitro studies have previously suggested that Salvia species are endowed with antimutagenic, antidiabetic, antiangiogenic, and gastroprotective properties. [32][33][34][35] The major polyphenols found in Salvia species include rosmarinic acid, caffeic acid, carnosol, and carnosic acid. 36 In another study, Fotovvat et al. 37 reported the occurrence of five phenolic compounds (rosmarinic acid, salvianolic acid A, salvianolic acid B, carnosic acid, and caffeic acid) at different concentration in the roots of 41 populations of 27 Salvia species. ...
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Objectives: Salvia verbenaca is a medicinal plant that has been traditionally used in Algeria for the treatment of wounds and emptied abscesses. The present study aimed to evaluate the cytotoxicity of methanolic extract of S. verbenaca roots and explore its ability to bestow protection against oxidative damage induced by H2O2 (200 μM). Materials and methods: The cytotoxic effects and protective properties of S. verbenaca on human monocytic leukemia cells (THP-1) was studied using thiazolyl blue tetrazolium bromide assay. The protective effects of the extract against H2O2-induced oxidative damage was evaluated using single cell gel electrophoresis (comet) assay and 2,7-dichlorodihydrofluorescien diacetate (H2DCFDA) assay. Results: S. verbenaca extract was found to be non-cytotoxic at concentrations <500 μg/mL. However, the use of 500 and 1000 μg/mL of the extract decreasedcell viability. H2DCFDA assay provided evidence for anti-oxidative properties of S. verbenaca. Addition of S. verbenaca (1 and 10 μg/mL) resulted in significant reductionin H2O2-induced reactive oxygen species (ROS) production. Further, comet assay showed that addition of the extract resulted in a significant reductionin the length and % DNA content of comet tail. Additionally,nuclei in the cells also appeared to be devoid ofdegradation. Conclusion: The use of S. verbenaca root extract conferred protection against H2O2-induced ROS production and DNA breakage in vitro.
... The suitability of Drosophila for detecting antigenotoxic effects of coffee, a complex mixture of bioactive compounds, was first demonstrated in our laboratory [83,84] using the somatic mutation and recombination test (SMART). Subsequently, many publications have shown the suitability of Drosophila for detecting antigenotoxic effects of crude mixtures of natural compounds [85][86][87]. Our studies were further strengthened by the similarity between the results of Drosophila and other in vivo and in vitro systems on antimutagenic effect and antioxidant activity of TP and BC. ...
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Background: The commonly consumed antioxidants β-carotene and tea polyphenols were used to assess their protective effects against γ-radiation induced sex-linked recessive lethal (SLRL) mutation and oxidative stress in Drosophila melanogaster. Third instar larvae and adult males of wild-type Oregon-K (ORK) were fed on test agents for 24 and 72 h respectively before exposure to 10Gy γ-irradiation. The treated/control flies were used to assess the induction of SLRLs. We also evaluated antioxidant properties of these phytochemicals in the third instar larvae. Results: Different stages of spermatogenesis in adult males showed a decrease in γ-radiation induced SLRL frequencies upon co-treatment with test agents. A similar trend was observed in larvae. Furthermore, a significant increase in antioxidant enzymatic activities with a decrease in malondialdehyde content was observed. Conclusion: β-carotene and tea polyphenols have exerted antigenotoxic and antioxidant effects in Drosophila. This study demonstrated the suitability of Drosophila as an alternative to mammalian testing for evaluating the antigenotoxic and antioxidant activity of natural products. Keywords: Drosophila melanogaster, γ-radiation, Tea polyphenols, β-carotene, Sex-linked recessive lethal mutations, Antioxidant enzymes, Alternative to mammalian testing
... Several reports indicated that the compounds responsible for antioxidative activity of S. officinalis ethanolic extract are mainly phenolic acids and flavonoids, namely rosmarinic acid, caffeic acid, carnosol, and carnosic acid [90,91]. The antioxidant activity and suppression of metabolic activation could be mechanisms through which sage or some of its components act as desmutagens [92]. The restoration of oxidative stress by improving the antioxidant defense system might be ascribed to the free radical scavenging/antioxidant properties of the phytochemical constituents present in S. officinalis [93]. ...
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Insecticides are believed to be the major factors behind the increase in agricultural productivity in the 20th century but their uses cause harmful effects on both animals and humans. Thus, the present work was designed to assess the preventive effect of Salvia officinalis and Ruta graveolens against chlorpyrifos- and methomyl-induced testicular and cardiac toxicities in rats. The rats orally administered 1/20 LD50 of either chlorpyrifos (13.8 mg/kg b.w.) or methomyl (1.6 mg/kg b.w.) 2 times for 4 weeks were co-treated with ethanolic extracts of Salvia officinalis and Ruta graveolens at dose level of 50mg/kg b.w. six days/week by oral administration for 4 weeks. The administration of chlorpyrifos and methomyl to rats induced testicular and cardiac toxicities that were evidenced by the histological deteriorated changes and the significant decrease in serum testosterone, FSH and LH levels as well as the significant increase in CK-MB, LDH and AST activities. Chlorpyrifos- and methomyl-administered rats exhibited a significant increase in testes and heart lipid peroxidation as well as a significant decrease in reduced glutathione content and superoxide dismutase, glutathione peroxidase and glutathione-S-transferase activities. Concomitant supplementation with Salvia officinalis or Ruta graveolens markedly prevented chlorpyrifos- and methomyl-induced biochemical and histopathological alterations. These findings provide evidence that Salvia officinalis and Ruta graveolens ethanolic extracts could prevent chlorpyrifos- and methomyl-induced testicular and cardiac toxicities in rats through potentiation of the antioxidant defense system.
... A second aim of the present study was also to determine the mutagenic potential of P. boldus and C. alba, as well any antimutagenic activity against the well-known alkylating mutagen agent ethyl methane sulphonate (EMS) using in vivo wing-spot test of D. melanogaster. It should be noted that D. melanogaster in vivo system assay was shown to be versatile and suitable for mutagenic and antimutagenic studies of various materials (Alaraby et al., 2016), including different medicinal plant extracts (Carmona et al., 2016a;Felício et al., 2011;Patenkovic et al., 2009) or their isolated bioactive components (Demir et al., 2010;Fatma et al., 2014). Finally, qualitative and quantitative analyses of phenolic and anthocyanin compounds and antioxidant capacities of P. boldus and C. alba leaf extracts were also determined. ...
Article
Peumus boldus Mol. (“Boldo”) and Cryptocarya alba Mol. Looser (“Peumo”) are medicinal shrubs with wide geographical distribution in South America. Their leaves and fruits are commonly used in traditional medicine because they exhibit natural medicinal properties for treatment of liver disorders and rheumatism. However, there are no apparent data regarding potential protective effects on cellular genetic components. In order to examine potential mutagenic and/or antimutagenic effects of these medicinal plants, the Drosophila melanogaster (D. melanogaster) wing-spot test was employed. This assay detects a wide range of mutational events, including point mutations, deletions, certain types of chromosomal aberrations (nondisjunction), and mitotic recombination. Qualitative and quantitative analyses of phenolic and anthocyanin compounds were carried out using biochemical and high-performance liquid chromatography methodologies. In addition, the antioxidant capacity of P. boldus and C. alba leaf extracts was also analyzed. P. boldus and C. alba extracts did not induce significant mutagenic effects in the D. melanogaster model. However, simultaneous treatment of extracts concurrently with the mutagen ethyl methane sulphonate showed a decrease of mutant spots in somatic cells of D. melanogaster, indicating desmutagenic effects in this in vivo model. Flavonoids and anthocyanins were detected predominantly in the extracts, and these compounds exerted significant antioxidant capacity. The observed antimutagenic effects may be related to the presence of phytochemicals with high antioxidant capacity, such as flavonoids and antohocyanins, in the extracts.
... 42 Its tea infusion reduces the frequency of mutations induced by methyl methanesulphonate in Drosophila melanogaster. 43 Its methanolic extract shows protective effect against cyclophosphamide-induced genotoxicity in rats. 44 This plant also reduces hydrogen peroxide-and dimethoxy-1,4-naphthoquinoneinduced oxidative DNA damage in HepG2 cells. ...
Article
Salvia officinalis (Sage) is a plant in the family of Labiatae/Lamiaceae. It is native to Middle East and Mediterranean areas, but today has been naturalized throughout the world. In folk medicine, S. officinalis has been used for the treatment of different kinds of disorders including seizure, ulcers, gout, rheumatism, inflammation, dizziness, tremor, paralysis, diarrhea, and hyperglycemia. In recent years, this plant has been a subject of intensive studies to document its traditional use and to find new biological effects. These studies have revealed a wide range of pharmacological activities for S. officinalis. Present review highlights the up-to-date information on the pharmacological findings that have been frequently reported for S. officinalis. These findings include anticancer, anti-inflammatory, antinociceptive, antioxidant, antimicrobial, antimutagenic, antidementia, hypoglycemic, and hypolipidemic effects. Also, chemical constituents responsible for pharmacological effects of S. officinalis and the clinical studies on this plant are presented and discussed.
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Organisms living in the real world are inevitably exposed to many chemical, physical, and biological agents that are harmful: food additives, natural toxins, pesticides, nanomaterials, metals, radiation, and viruses, among others. However, most of these agents, if not all, may have unexpected consequences on the biota. Organisms are continuously exposed to heterogeneous xenobiotics released into different habitats either deliberately, inadvertently, or through non-regulated industrial discharges. Understanding how these agents can produce genetic alterations in DNA and what their role is in different biological systems continue to receive intense attention in fields such as health, pharmaceutical, environment, industry, agriculture, and food sectors. Mutagenicity denotes the generation of stable changes in the DNA molecule that differ from the normal sequence of an organism, which may result in a transmissible change in the genotype of living organisms. Any damaged genetic material could result in mutations, thus stimulating carcinogenic progression or establishing a framework for hereditary disorders. Whereas mutations are generated mainly by exogenous agents, named mutagens, the term genotoxic describes the capability of those chemical, physical, and biological agents to directly affect the structure of DNA, the cellular spindle apparatus, and/or the topoisomerase enzymes that modulate DNA topology during DNA replication as well as chromosome segregation, which are, finally, responsible for the fidelity of the genome. However, genotoxic damage to DNA is not always associated with mutations. Spontaneous mutations arise from a variety of sources due to errors in DNA replication, repair, and recombination, and the presence of transposable genetic elements. Many agents can produce chemically reactive species during their metabolism, or are themselves reactive and may, therefore, cause irreversible changes to DNA. Heritable changes are the origin of innate metabolic deficiencies in cellular systems, generating morbidity and mortality in organisms. Genetic disorders can be produced by a mutation in only one or in multiple genes, through a combination of gene mutations and environmental factors or by damage at the chromosomal level that affects the number and/or structure of entire chromosome(s), or parts thereof. Mutations in cells are not only involved in the initiation and promotion of several human diseases, including cancer, but are also implicated in several genetic disorders, like anaemia, diabetes, cardiovascular alterations, obesity, atherosclerosis, and numerous other degenerative disorders. Currently, scientists recognize more than 4,000 human diseases that are produced by mutations as a result of a combinatorial failure of more than one of these processes. As indicated in a book we published some years ago, entitled “Genotoxicity-A Predictable Risk To Our Actual World”, without knowledge of the mutagenic and genotoxic properties of chemical, physical, and biological agents, the evaluation of responses in living organisms, including humans, is difficult, and consequently the regulation of genotoxicants is a complex and difficult process. Accurate identification of the different classes of environmental genotoxicants and mutagens IV would permit international regulatory scientific agencies to use this information in a variety of legislative decisions to establish priorities of public and scientific concern. We have attempted to compile information from different fields, highlighting the detrimental influence that mutagenic and genotoxic agents inflict on DNA and how antimutagenic and anticarcinogenic modulators are able to reduce the negative impact of such toxic agents on living species. Antimutagens and anticarcinogens are agents that decrease the number of mutations in cells, modulating host defence mechanisms. Therefore, knowledge regarding the mechanism of action of potentially mutagenic and/or carcinogenic agents provides the basis for elucidation of how these protective chemicals exert a response. Antimutagens are employed as one of the key methods to increase cellular resistance to mutagens. They are able to reduce or even remove the mutagenic effects exerted by toxic xenobiotics, stimulating compensatory repair and tolerance pathways in the DNA. In regard to their mode of action, antimutagens can act by influencing different targets, such as cellular membranes, DNA damage repair, replication, chromatin organization, and cell signalling. This book opens with an interesting discussion about the use of yeast as a model organism for studying the biological effects of the P450-mediated metabolism of xenobiotics. This chapter also focuses on strategies for employing multiple genetic endpoints in screening chemicals, yeast strains that facilitate phenotyping cytochrome P450 polymorphisms to test the safety of thousands of chemicals, the limitations of animal systems, the advantages of model organisms, and the humanization of yeast cells by expressing human cytochrome P450 genes. The second chapter describes a possible molecular mechanism for how the addition of exogenous polyamines may increase the production of improved strains of filamentous fungi and the biotechnological applications of this phenomenon. The third chapter provides information on chemical and physical mutagenesis in breeding, exemplified by new modern homozygous self-pollinated sunflower lines, as well as additional recommendations on the use of methods to induce mutagenesis, including methods of generation, investigation, and subsequent use of mutations. The fourth chapter comprises an excellent review comparing the specific toxicity and genotoxicity exerted by heavy metals such as lead and cadmium using mammalian cells as a biological matrix in the context of ecotoxicology. The fifth chapter describes the importance of doublecortin-like kinase 1 (DCLK1), a member of the protein kinase superfamily and the doublecortin family, and its role in DNA damage response and repair, via direct and indirect mechanisms. It is well known that DCLK1 is expressed in cancer stem cells, and is implicated in initiating tumours. The sixth chapter reviews the role of oxidative stress induced by vanadium (a common mechanism of action of metal pollutants), observed in in vivo and in vitro systems, highlighting the way the production of free radicals inflicts damage in biomolecules including DNA, proteins, lipids, and carbohydrates. In addition, the chapter emphasizes the protective role of two water-soluble antioxidants, namely carnosine and ascorbate, present in biological systems. The seventh chapter constitutes an update on how the w-/w+ somatic mutation and recombination test of Drosophila melanogaster are employed extensively for antigenotoxicity analysis, focusing on actual published results to aid in the development of a reliable protocol in antigenotoxicity. Finally, this book comprises a chapter discussing the properties of antimutagenic substances with multiple mechanisms of action, in addition to introducing different aspects of natural and synthetic antimutagens. XIV V Further, the chapter includes a brief compilation of scientific findings, either from dietary sources or synthetic agents, with potential to combat the disorders caused by the mutagenic agents, noting possible future perspectives and mechanisms of antimutagenics. The editors of Genotoxicity and Mutagenicity - Mechanisms and Test Methods are enormously grateful to all contributing authors for sharing their knowledge and insights in this book. They have made an extensive effort to gather the information included in every chapter. Readers are challenged to interpret the significance of various mechanisms and tested methodologies for detecting the causes and consequences of mutagenic and genotoxic agents. We hope that the topics discussed here encourage all those interested to explore new aspects of the fields of mutagenesis and genotoxicity by stimulating scientific dialogue. The publication of this book is of great importance to scientists, biologists, pharmacologists, physicians, and veterinarians, as well as engineers, teachers, graduate students, and administrators of environmental programmes, who can make use of these investigations to understand some aspects of mutagenic and genotoxic issues, making this volume a valuable reference in the future.
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Salvia officinalis is one of the most valued herbs because of its high amount of essential oil and its many components. It has many health-related uses such as improving cognition, as well as reducing the amount of nursing mother's milk during weaning, also recommended for the gargling of the infectious throat, and to treat cardiovascular diseases and nervous disturbance, depression, cerebral ischemia and acts as an antiseptic for wounds. This study aim was to prepare the plant extract of Salvia officinalis L. from the Iraq local areas, determine its chemical properties and study its effect on some physiological and immunological variables in white rats. The plant leave Extract was Prepared and its effects were assessed on several physiological parameters using 20 male rats. The rats were divided into four groups. the control group(G1) received standard food and water; the negative control group (G2) received fat rich diet; G3 rats were given Salvia officinalis with a concentration of 100 mg\ kg\day. G4: rats were given Salvia officinalis 100mg/kg body weight and received fat rich diet. Roche/Hitachi, cobas c 501/502 were used to evaluate the levels of aminotransferase Enzymes, Aspartate transaminase (AST), Alanine aminotransferase (ALT), alkaline phosphatase enzyme (ALP), serum creatinine, serum urea, total protein, albumin, cholesterol, triglyceride, and high-density lipoprotein (HDL). While Globulin concentration, very Low-Density Lipoprotein (VLDL), and Low-Density Lipoprotein (LDL) were calculated according to some referred equations. The phytochemical analysis showed that the compounds identified in the sample were found to be alkaloids, phenols, tannins, coumarins glycosides, flavonoids, quinines, Carbohydrates and steroids. The results showed a significant increase (P <0.01) in the level of liver enzymes ALT, AST and ALP, in the G2 treated with the high fat diet compared with a control group and showed a significant increase (P <0.01) in the level of urea an
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Antioxidants have been classically employed in the food industry and elsewhere, mainly as preservatives. Further to this deed, antioxidants are nowadays increasingly sought as components of the diet owing to their benefits upon human health – via protection of cells against oxidative stress, which might otherwise lead to cell damage and death; coronary heart diseases, ulcers, cancers and neurogenerative diseases – besides overall ageing, are but a few examples of diseases and health conditions that can be prevented (or, at least, delayed) via regular and balanced ingestion of antioxidants. Antioxidants can be chemically synthesized, or else extracted from biological samples – especially from plants. Natural antioxidants have been in greater and greater demand, in response to a more environmentally-aware consumer population. The most abundant antioxidants in plants are polyphenols; deprived of nitrogen, these arenes substituted by hydroxyl groups possess more than one phenol ring, and are mainly generated via the shikimate pathway or the acetate pathway. This chapter reviews the most important literature sources pertaining to wild plants from which extracts have been obtained that possess antioxidant capacity; wild plants from the Mediterranean area are discussed as a case study towards this endeavor. The mechanisms of antioxidant action in biological systems are briefly considered, as well as the analytical assays available to detect and quantitate them.
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Grifola gargal is an edible mushroom with attributed antioxidant properties. Different sources of G. gargal materials, i.e., fruit bodies and mycelia grown in liquid or solid media, were used to study its potential protective capacity when somatic mutation and recombination is induced in Drosophila melanogaster using DMBA (7-12-dimethyl-benz(α)anthracene) as promutagen. Heterozygote larvae (white/white+) were grown in media with different concentrations of DMBA. Grifola gargal fruit bodies (GgFB) or mycelia from liquid culture (GgLC) or from solid culture (GgWG), i.e., biotransformed wheat kernel flour, were added to the culture media in combined treatments with DMBA. Water, DMBA solvent, or wheat flour (WF) plus DMBA solvent were used as negative controls. Larval mortality increased from 9% to 11% in negative controls to 31% to 36% in DMBA treatments. The addition of GgFB, GgLC, or GgWG materials produced a protective effect on 25 μmol/vial DMBA-induced mortality. Mutations observed in SMART, as light spots per 100 eyes (LS/100 eyes), increased with increasing doses of DMBA; this was also true when considering the mutation incidence expressed as percentage of eyes exhibiting light spots (% eyes with LS). Interestingly, mycelia from GgFB, GgLC, or GgWG, in the presence of 25 μmol/vial DMBA, showed lower values in SMART of both the total LS/100 eyes and the percentage of eyes with LS. Thus, Grifola gargal materials were not only nontoxic, but in combination with 25 μmol/vial DMBA lowered the mortality induced by the promutagen and showed antimutagenic effects. Protective effects of G. gargal against DMBA are discussed in terms of the onset of desmutagenic and/or bioantimutagenic mechanisms of detoxification in the host organism, probably due to some bioactive compounds known to occur in higher mushrooms.
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The effect of culinary-medicinal Royal Sun Agaricus (Agaricus brasiliensis) hot water extract on methyl methane sulfonate (MMS) induced mutagenicity/genotoxity in Drosophila melanogaster was studied using a quick and broadly applicable in vivo assay, i.e., the wing somatic mutation and recombination test. We used 2nd instar larvae, trans-heterozygous for the third chromosome recessive markers, i.e., multiple wing hairs (mvh) and flare-3 [flr (3)], and fed them for 24 h with the aqueous extract of A. brasiliensis. For antigenotoxicity studies a 24-h pretreatment with the extract was done, followed by a 48-h treatment of the then 3rd instar larvae with MMS. The frequency of mutations of the wing blade changes (i.e., of the number of wing spots of different sizes) induced in somatic cells was determined as a parameter of genetic changes of the wing imaginal discs. The results showed that A. brasiliensis extract did not cause any genotoxic or mutagenic effects. No antigenotoxic and/or protective effect against the induction of mutations by MMS was observed. Instead, a possible enhanced mitotic recombination frequency by MMS was seen after pretreatment of the larvae with A. brasiliensis extract. Possible mechanisms of action are discussed.
Article
The use of electron spin resonance (ESR) spectroscopy to accurately distinguish irradiated from unirradiated sage tea was examined. Before irradiation, sage tea samples exhibit one asymmetric singlet ESR signal centered at g=2.0037. Besides this central signal, two weak satellite signals situated about 3mT left and right to it in radiation-induced spectra. Irradiation with increasing doses caused a significant increase in radiation-induced ESR signal intensity at g=2.0265 (the left satellite signal) and this increase was found to be explained by a polynomial varying function. The stability of that radiation-induced ESR signal at room temperature was studied over a storage period of 9 months. Also, the kinetic of signal at g=2.0265 was studied in detail over a temperature range 313–353K by annealing samples at different temperatures for various times.
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Salvia officinalis L. (sage) is an important industrial plant used both for food and pharmaceutical purposes. The terpene fraction of this plant is responsible for many of its therapeutic and culinary properties. We used different extraction methods Tenax TA® purge and trap, headspace solid-phase microextraction (HS-SPME), headspace sorptive extraction (HSSE), and stir bar sorptive extraction (SBSE) to analyse the terpene fraction extracted from sage tea by GC-MS. 20 compounds were identified, including α-thujone, β-thujone and several other oxygenated monoterpenes (1,8-cineole, linalool, camphor, boneol and bornyl acetate) and oxygenated sesquiterpenes (caryophyllene oxide, viridiflorol, humulene epoxide I, II and III). Tenax TA® and HSSE extracted a lower number of identified compounds, whereas HS-SPME allowed the complete extraction of volatiles, with particular reference to α-thujone and β-thujone. The importance of the determination of thujones content in sage herbal tea is also discussed. This article is protected by copyright. All rights reserved.
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Genotoxicity studies often involve studies with test substances dissolved in polar aprotic solvents such as dimethyl sulfoxide (DMSO). However, it is well known that DMSO has toxic properties, thus it can affect the results of performed studies, both in vitro and in vivo, and in the end their validity. In order to eliminate such doubts, DMSO toxicity testing must be performed on the model organism before its application as a solvent in the study. Our goal was to determinate the LC50, NOEC and LOEC values for DMSO on Drosophila melanogaster larvae. Twelve concentrations of DMSO were tested in duplicates and each experimental group consisted of thirty larvae which were three-day old. After 12 days of exposure, number of live hatched adults was counted, Risk Assessment software tool (RA V1.0) and probit analysis were utilized in order to calculate values for LC50, LOEC, and NOEC. It was determined that LC50 is 0.42% v/v, LOEC 0.04% v/v, and NOEC is ˂ 0.04% v/v. Confidence intervals (95%) were also calculated. These results suggest that DMSO is more toxic to D. melanogaster larvae than it was initially thought. Keywords: DMSO, toxicity, Drosophila melanogaster, NOEC, LOEC, LC50
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Genotoxicological studies are emerging as fundamental for knowing the hazards to our genome, to our health. Drosophila melanogaster is one of the preferable organisms for toxicological research considering its metabolic similarities (viz. on dietary input, xenobiotic metabolizing system, antioxidant enzymes and DNA repair systems) to mammals. Accordingly, somatic mutation and recombination tests (SMARTs) of D. melanogaster are fast and low-cost in vivo assays that have shown solid results evaluating genotoxicity. The w/w + SMART uses the white (w) gene as a recessive marker to monitor the presence of mutant ommatidia (eye units), indicating the occurrence of point mutations, deletions, mitotic recombination or/and nondisjunction. Additionally, several studies used SMARTs to assess antigenotoxicity, with some using the w/w + SMART. We reviewed the state of the art of the w/w + SMART used for antigenotoxicity analysis, focusing on published results, aiming to contribute to the conception of a reliable protocol in antigenotoxicity. As such, genotoxic agents with known action mechanisms, as streptonigrin (oxidative stress inducer), were used as a genotoxic insult for proving the antigenotoxic effects of natural substances (e.g. seaweeds), demonstrating the presence of antimutagens in their composition. These antigenotoxicity studies are crucial for promoting preventive measures against environmental genotoxics that affect humans daily.
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The main objective of our present work was to ascertain the efficacy of Drosophila melanogaster model for assessing antigenotoxic and antioxidant effects of dietary phytochemicals gallic acid (GA), quercetin (QC) and limonene (Lim) against urethane (URE), a genotoxic environmental carcinogen. Oregon-K (ORK) adult male flies were fed GA, QC and Lim in combination with URE (20mM) in 10% sucrose for 72h. Third instar larvae were fed instant medium containing the above phytochemicals and URE for 24h. Sex-linked recessive lethal test (SLRL) and assays for estimating glutathione content (GSH), glutathione S- transferase (GST), catalase (CAT), superoxide dismutase (SOD) and lipid peroxidation (MDA content) were performed. Adult feeding experiments demonstrated that co-treatment of flies with URE and the test phytochemicals has significantly decreased the frequencies SLRL mutations in all the germ cell stages when compared to that with URE alone. Larval feeding experiments also showed a similar pattern. The above results correlate well with antioxidative potentials of the test agents where we observed the elevated enzymatic levels with a significant reduction in MDA level in Drosophila larvae. The results further suggest that the dietary phytochemicals have an antioxidant and antimutagenic property which can be assessed using Drosophila melanogaster.
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Coriander is a strongly aromatic, erect, herbaceous annual herb with strong antioxidant activity and this antioxidant activity correlated well with the phenolic compounds. This chapter describes the botany, history, producing regions, flavor and aroma, parts used, and active constituents. The chapter also highlights the uses of coriander in different recipes around the world. Coriander has been reported to have antibacterial, spasmolytic, stomachic, carminative, antimicrobial, antifungal, cholesterol-lowering, anti-inflammatory, and antioxidant properties. Finally the medicinal uses, functional properties, and antioxidant properties of coriander are discussed in great detail.
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Sage is an evergreen perennial shrub with strong antioxidant properties. This chapter describes the botany, history, producing regions, flavor and aroma, parts used, and active constituents. The chapter also highlights the uses of sage in different recipes around the world. Sage has been reported to have antiseptic, antimicrobial, anticancer, antiproliferative, antidiabetic, anti-inflammatory, and antioxidant properties. Finally the medicinal uses, functional properties, and antioxidant properties of sage are discussed in great detail.
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Nanoparticles derived from plants known for their high content of flavonoids provide a biologically inspired route to design therapeutic agents and a means of reducing metal nanoparticle toxicity. Little is currently known on the anti-neurotoxicity of Salvia officinalis L. extracts and their corresponding nanoparticles. In the present study, anti-neurotoxic stress activity of S. officinalis extract obtained from aerial parts (leaves) and nanoparticles derived from these extract were investigated against Methylmercury (MeHg). Ten groups of rats were treated with different concentrations of extracts (125 mg/kg bw of non-nanoparticles of S. officinalis, SO; 25, 50 and 125 mg/kg bw of SO nanoparticles, SON) and/or MeHg (10 mg/kg bw) for 8 weeks to determine their anti-neurotoxic effect. After the last injection, rats were sacrificed and brain capsule were collected on ice bath and the cortex were separated in order to investigate the apoptosis, reactive oxygen species (ROS), expression alteration of glutamate transporters (GLAST, GLT-1, SNAT3 and ASCT2 mRNA), DNA fragmentation, 8-OHdG levels and glutathione peroxidase (GPx) activity. The preset study found that the neurotoxic stress of MeHg was markedly inhibited with SO extracts especially with SO nanoparticles. Treatment of male rats with SON50+MeHg decreased significantly the apoptosis rate, ROS production, DNA fragmentation and 8-OHdG levels as well as increased the expression of GLAST, GLT-1, SNAT3, ASCT2 mRNA and GPx activity in the cerebral cortex. The biosynthesized nanoparticles may be further characterized to better evaluate their anti-neurotoxicity potential against other neurotoxic agents.
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Rapid progress in biomedical fields and development of new technologies in bioengineering and tissue engineering, such as 3D bioprinting technologies, lead us to extensive and rapid designing of new biomaterials and medical devices (MDs). The main feature that newly engineered biomaterials must possess, in order to be applied in clinical practice, is to be biocompatible. Besides toxicity testing, genotoxicity and mutagenicity assays are very important in assessment of biocompatibility. Genotoxicity/mutagenicity is a feature that can completely disable the use of some biomaterial and MDs in biomedical and clinical applications especially if material is intended for long term use. Mutagens are agents that can cause heritable changes in DNA and their capacity to cause mutations is defined as mutagenicity. Genotoxicity is a wider term which, besides mutagenicity, refers to the property of an agent to cause various damages to DNA and other disturbances which can affect genes function. In this chapter, we gave an overview of in vitro and in vivo assays that are mostly used in biocompatibility assessment with a focus on the most promising assays for evaluations of genotoxicity and mutagenicity of biomaterials.
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Fennel, mint (peppermint), and sage herbal teas and apple, lemon, and rosehip fruit teas were selected for the determination of the following risk elements contents: aluminium (Al), arsenic (As), barium (Ba), cadmium (Cd), nickel (Ni), lead (Pb), and antimony (Sb). Moreover, the effect of lemon on these elements contents was also examined. Inductively Coupled Plasma Optical Emission Spectrometry (ICP-OES) was used for these experiments on selected teas (2 g of tea infused in 100 ml of water). The maximum changes of elements concentrations after the lemon addition were as follows: Al 1077 μg/l in lemon tea; Ba 12560 μg/l in rosehip tea; Cd 183 μg/l in sage tea; Ni 1136 μg/l in fennel tea; and Pb 238 μg/l in lemon tea. Both As and Sb were below the detection limits in pure tea and lemon-infused teas. This study indicated that after the lemon addition, rosehip tea had a hazard index (HI) value of 10827 × 10-4 for 200 ml/day (2 cups/day), which represents a high risk for human health. If lemon is added to rosehip tea for consumption, 100 ml/day is recommended according to the calculated HI values.
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Dimethyl sulfoxide (DMSO) is commonly used as a solvent for organic compounds but its toxic properties can affect both in vitro and in vivo studies. Thus, evaluation of DMSO toxicity must be performed on the model organism before its application as a solvent in the target studies. Present study aimed to determine the lethal concentration required to kill 50% of the population in a given period of time (LC50), no observed effect concentration (NOEC), and lowest observed effect concentration (LOEC) values for DMSO on Drosophila melanogaster which is frequently used as a model for toxicity studies. Twelve different concentrations of DMSO were tested on three-day old D. melanogaster larvae for 12 days. At the end of the life cycle, number of live hatched adults and un-hatched pupae were counted. Based on probit analysis 12 days LOEC was 0.04% v/v, 12 days NOEC was ˂ 0.04% v/v and 12 days LC50 was 0.42% v/v. The results indicate that DMSO may be more toxic to D. melanogaster than it was initially considered.
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Mutagenic and antimutagenic potential of essential oil (EO) of cultivated sage (S. officinalis L.) and its monoterpenes: thujone, 1,8-cineole, camphor and limonene against UVC-induced mutations was studied with Salmonella/microsome, E. coli WP2, E. coli K12 [Simić, D., Vuković-Gačić, B., Knežević-Vukčević, J., 1998. Detection of natural bioantimutagens and their mechanisms of action with bacterial assay-system. Mutat. Res. 402, 51–57] and S. cerevisiae D7 reversion assays. The toxicity of EO differed, depending on the strain used. The most sensitive were permeable strains TA100, TA102, E. coli K12 IB112 and non-permeable WP2. Mutagenic potential of EO and monoterpenes was not detected, with or without S9. EO reduced the number of UV-induced revertants in a concentration-dependent manner, reaching 50–70% of inhibition at the maximum non-toxic concentrations: 3 μl/plate (TA102), 5 μl/plate (WP2), 7.5 μl/plate (IB112), 30 μl/plate (E. coli K12 SY252) and 60 μl/plate (D7). The metabolic activation had no effect on antimutagenic potential of EO. Similar toxicity of monoterpenes was observed in TA100, E. coli SY252 and D7, with the exception of limonene (less toxic to D7). Reduction of UV-induced revertants by non-toxic concentrations of monoterpenes, tested with SY252 and D7, reached 40–50% at 15–20 μl/plate of thujone, 10 μl/plate of cineole and 1–10 μg/plate of camphor. Limonene showed antimutagenic effect only in D7. Our data recommend sage monoterpenes for further chemoprevention studies.
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The antioxidant activities of the sage polyphenols, consisting of flavone glycosides and a range of rosmarinic acid derivatives, were evaluated for their capacity to scavenge DPPH and superoxide anion radicals and also to reduce Mo(VI) to Mo(V). The rosmarinic acid derivatives all showed potent antioxidant activity in three test systems and their capacity to reduce Mo(VI) to Mo(V) and their superoxide radical scavenging activities, with values ranging from 220 to 300 SOD units/mg, in particular, were 4–6 and 15–20 times greater than trolox, respectively. The high SOD activity of rosmarinic acids could be attributed to the radical-scavenging catechols and the xanthine oxidase-inhibiting caffeic acid moieties contained in them. The antioxidant activity of the flavonoids was variable and those with a catechol B-ring (luteolin glycosides) were more active than those without (apigenin glycosides).
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The fly Drosophila melanogaster is one of the most intensively studied organisms in biology and serves as a model system for the investigation of many developmental and cellular processes common to higher eukaryotes, including humans. We have determined the nucleotide sequence of nearly all of the ∼120-megabase euchromatic portion of theDrosophila genome using a whole-genome shotgun sequencing strategy supported by extensive clone-based sequence and a high-quality bacterial artificial chromosome physical map. Efforts are under way to close the remaining gaps; however, the sequence is of sufficient accuracy and contiguity to be declared substantially complete and to support an initial analysis of genome structure and preliminary gene annotation and interpretation. The genome encodes ∼13,600 genes, somewhat fewer than the smaller Caenorhabditis elegansgenome, but with comparable functional diversity.
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The inhibition of spontaneous and UV-induced mutations by essential oil (EO) of sage (Salvia officinalis L.) and its fractions F1-F5 containing different proportions of mono- and sesquiterpenes was studied with the Salmonella/microsome, E. coli K12, and S. cerevisiae D7 reversion assays. The EO, F1, and F2 exhibited antimutagenic potential against UV-induced mutations in all tests. Fractions F3 and F4 produced a toxic, mutagenic, or antimutagenic response, depend­ing on the test organism used. Reduction of spontaneous and UV-induced mutations by F5 was detected only in permeable strains of E. coli. The obtained results demonstrate antimutagenic activity of volatile sage terpenes and recommend them for further antimutagenesis and anticarcinogenesis studies.
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A comparative analysis of the genomes of Drosophila melanogaster, Caenorhabditis elegans, and Saccharomyces cerevisiae-and the proteins they are predicted to encode-was undertaken in the context of cellular, developmental, and evolutionary processes. The nonredundant protein sets of flies and worms are similar in size and are only twice that of yeast, but different gene families are expanded in each genome, and the multidomain proteins and signaling pathways of the fly and worm are far more complex than those of yeast. The fly has orthologs to 177 of the 289 human disease genes examined and provides the foundation for rapid analysis of some of the basic processes involved in human disease.
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Tamoxifen (TAM) is an anti-oestrogen used for treatment and prevention of human breast cancer, but it is also related to human endometrial and uterine cancer. The wing spot test in Drosophila melanogaster was employed to determine the genotoxic effects of TAM and 4-nitroquinoline-1-oxide (4-NQO), a carcinogen that produces adducts similar to TAM-DNA adducts detected in rodent liver and human liver microsomes. As Drosophila spp. have no oestrogen receptor, no effects can result in binding of TAM to a receptor. Chronic treatments with TAM citrate were performed with 3-day-old larvae of the standard (ST) and high bioactivation (HB) crosses of the wing spot test at concentrations of 0.66, 1.66 and 3.33 mM. In addition, the carcinogen 4-NQO was administered at 2.5 and 5.0 mM. Somatic spots on normal wings from marker-heterozygous flies and on serrate wings from balancer-heterozygous flies were scored to determine mutation and recombination events in somatic cells for each compound. The results showed genotoxic effects of TAM at 1.66 and 3.33 mM in the ST cross only and without a clear dose-response effect. This suggests a weak genotoxicity of this anti-oestrogen. The negative results obtained with TAM in the HB cross may indicate efficient detoxification of the compound by the increased xenobiotic metabolism present in this cross. As reported before, 4-NQO showed genotoxic effects in the ST cross with a clear dose-response effect. For the first time, we report enhanced effects of this compound in the HB cross. It is concluded that the genotoxicity of TAM in the Drosophila wing spot test is different from that of 4-NQO.
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Caffeic acid, rosmarinic acid and oligomers of caffeic acid with multiple catechol groups are all constituents of Salvia officinalis. Their antioxidant potential was investigated with regard to their radical scavenging activity and the stability and structure of the intermediate radicals. Pulse-radiolytic studies revealed very high rate constants with hydroxyl radicals. Evidence from kinetic modeling calculations suggested an unusual complex behavior due to the presence of both O4- and O3-semiquinones and formation and decay of a hydroxyl radical adduct at the vinyl side chain. The radical structures observed by EPR spectroscopy after autoxidation in slightly alkaline solutions were only partially identified due to their instability and generally represented dissociated O4-semiquinones. Hybrid density-functional calculations of the potential radical structures showed distinct differences between the resonance stabilization of the O4- and O3-semiquinones of caffeic and dihydrocaffeic acids, reflected also in the considerably faster decay of the O3-semiquinone observed by pulse radiolysis. No evidence was found for dimerization reactions via Cbeta radicals typical for lignin biosynthesis.
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Naturally occurring antimutagenic factors, especially those of plant origin, have recently become a subject of intensive research. Antimutagenic properties of terpenoid fractions of sage (Salvia officinalis) were tested in mammalian system in vivo through examining the ability of sage to decrease the frequency of aberrant cells induced by a potent mutagen. First, groups of mice were treated with three concentrations of sage alone and it was established that the frequency of aberrant cells after treatment with a concentration of 25 microL/kg was not significantly different from the negative control (olive oil), while that found after treatment with the 50 microL/kg concentration differed significantly (chi2(1) = 4.05, p < 0.05). Sage used at a concentration of 100 microL/kg was cytotoxic. Mitomycin C (MMC), known as a potent mutagen, was used for induction of chromosome aberrations. Post-treatment with sage suppressed the effects of MMC significantly. Both concentrations (25 microL/kg and 50 microL/kg) produced a significant decrease in the frequency of aberrations relative to MMC (chi2(1) = 5.42, p < 0.02, chi2(1) = 14.93, p < 0.001, respectively). The percent of aberrations decreased with increasing concentrations of sage. Only nontoxic concentrations of sage without mutagenic effects can be recommended for use as inhibitors of mutagenesis or carcinogenesis.
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In this study, different concentrations of some organophosphate insecticides (methyl parathion, azamethiphos, dichlorvos and diazinon) have been evaluated for genotoxicity in the wing somatic mutation and recombination test (SMART) of Drosophila melanogaster. Third-instar larvae trans-heterozygous for two genetic markers mwh and flr, were treated at different concentrations (1 ppm, 3 ppm, 5 ppm, 7 ppm, 10 ppm) of the test compounds. A positive correlation was observed between total mutations and the number of wings having mutations. In addition, the observed mutations were classified according to size and type of mutation per wing. Chemicals used were ranked in decreasing order according to their genotoxic effects as diazinon, dichlorvos, methyl parathion, azamethiphos.
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Common sage (Salvia officinalis L.) is among the plants that are claimed to be beneficial to diabetic patients, and previous studies have suggested that some of its extracts have hypoglycaemic effects in normal and diabetic animals. In the present study, we aimed to verify the antidiabetic effects of an infusion (tea) of common sage, which is the most common form of this plant consumed. Replacing water with sage tea for 14 d lowered the fasting plasma glucose level in normal mice but had no effect on glucose clearance in response to an intraperitoneal glucose tolerance test. This indicated effects on gluconeogenesis at the level of the liver. Primary cultures of hepatocytes from healthy, sage-tea-drinking rats showed, after stimulation, a high glucose uptake capacity and decreased gluconeogenesis in response to glucagon. Essential oil from sage further increased hepatocyte sensitivity to insulin and inhibited gluconeogenesis. Overall, these effects resemble those of the pharmaceutical drug metformin, a known inhibitor of gluconeogenesis used in the treatment and prevention of type 2 diabetes mellitus. In primary cultures of rat hepatocytes isolated from streptozotocin (STZ)-induced diabetic rats, none of these activities was observed. The present results seem to indicate that sage tea does not possess antidiabetic effects at this level. However, its effects on fasting glucose levels in normal animals and its metformin-like effects on rat hepatocytes suggest that sage may be useful as a food supplement in the prevention of type 2 diabetes mellitus by lowering the plasma glucose of individuals at risk.
Article
A comparative analysis of the genomes ofDrosophila melanogaster, Caenorhabditis elegans, and Saccharomyces cerevisiae—and the proteins they are predicted to encode—was undertaken in the context of cellular, developmental, and evolutionary processes. The nonredundant protein sets of flies and worms are similar in size and are only twice that of yeast, but different gene families are expanded in each genome, and the multidomain proteins and signaling pathways of the fly and worm are far more complex than those of yeast. The fly has orthologs to 177 of the 289 human disease genes examined and provides the foundation for rapid analysis of some of the basic processes involved in human disease.
Article
The ability of ascorbic acid (Vitamin C) to modulate the genotoxic action of several mutagens was investigated in the wing spot test of Drosophila melanogaster. In this assay, 3-day-old transheterozygous larvae for the multiple wing hairs (mwh, 3-0.3) and flare (flr, 3-38.8) genes were treated with three reference mutagenic compounds, namely cobalt chloride (CoCl2), 4-nitroquinoline 1-oxide (4-NQO) and potassium dichromate (K2Cr2O7). The results obtained show that the three reference mutagens tested were clearly genotoxic in the Drosophila wing somatic mutation and recombination test (SMART). None of the three concentrations tested of ascorbic acid (25, 75 and 250mM) induced significant increases in the frequency of the mutant clones recorded. When co-treatment experiments with ascorbic acid were carried out, different results were found. Thus, ascorbic acid was effective in reducing the genotoxicity of K2Cr2O7 virtually to the control level; on the contrary, it did not show any antigenotoxic effect on the genotoxicity of 4-NQO. Finally, co-treatments with CoCl2 and ascorbic acid show a significant increase in the frequency of mutant clones over the values obtained with CoCl2 alone.
Article
Evidence is provided that ascorbic acid (vitamin C), when used as a pretreatment, protects against mutation/recombination induced by γ-rays and chromium (VI) oxide in mwh+/+flr3 larvae in the wing spot test in Drosophila
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Ten phenolic compounds were isolated from a butanol fraction of sage extracts. Their structures were determined by spectral methods (NMR, MS, IR). Among them, a novel compound, 4-hydroxyacetophenone-4-O-β-d-apiofuranosyl-(1→6)-O-β-d-glucopyranoside, was identified. Two test systems, DPPH free radical scavenging activity and radical cation ABTS•+ scavenging activity, were used to evaluate their antioxidant activity. The most active compounds were found to be rosmarinic acid and luteolin-7-O-β-glucopyranoside. Keywords: Sage; Salvia officinalis; phenolic compounds; antioxidant activity
Article
The antioxidant compounds of oleoresin of sage (Salvia officinalis) were separated by column chromatography and high-performance liquid chromatography. Six major compounds were purified and identified by IR, MS, and H-1 NMR spectrometry as carnosol, carnosic acid, rosmadial, rosmanol, epirosmanol, and methyl carnosate. Their antioxidative activity was measured with an accelerated test, and their content was quantified in sage and in four commercial rosemary extracts.
Article
The wing Somatic Mutation And Recombination Test (SMART) in Drosophila melanogaster was used to study the modulating action of vanillin (VA) in combination with the alkylating agents mitomycin C (MMC), methylmethanesulphonate (MMS) and the bifunctional nitrogen mustard (HN2). Two types of treatments with VA and each of the three genotoxins were performed: chronic co-treatments of three-day-old larvae of the standard cross as well as post-treatments after acute exposure with the genotoxins. This allowed the study of the action of VA not only in the steps that precede the induction of DNA lesions but also in the repair processes. The overall findings from the co-treatment series suggest that ingestion of VA with MMS or MMC can lead to significant protection against genotoxicity; but this is not the case with HN2. Antioxidant activity, suppression of metabolic activation or interaction with the active groups of these two alkylating agents could be mechanisms by means of which VA exerts its desmutagenic action. In contrast, when evaluated in the post-treatment procedure, VA causes two antagonistic effects on the genotoxicity of MMC: (i) synergism on recombination (172.8%) and (ii) protection against mutation (79.0%). Consequently, both activities together lead to a considerable increase in mitotic recombination. In spite of being separate events, recombination and gene mutation are correlated during mitosis since the fate of a DNA lesion depends on the repair pathway followed. Our results may suggest that VA is a modifying factor that blocks the mutagenic pathway and consequently directs the MMC-induced lesions into a recombinational repair. Furthermore, VA did not modify the genotoxicity when administered after treatments with HN2 or MMS. Therefore, the major finding of the present study, namely the co-recombinagenic activity of VA on MMC-induced lesions, seems to be related to the type of induced lesion and consequently to the repair processes involved in its correction.
Article
The anti-genotoxic action of turmeric was evaluated by Somatic Mutation and Recombination Test (SMART). As described in other mutagenecity tests, turmeric showed non mutagenic effects in the SMART. The well known powerful mutagen urethane was used as a model to evaluate the anti-genotoxicity of turmeric. Combined treatment of urethane and turmeric displayed, throughout all concentrations assayed, an inhibition of the genotoxic effect of urethane by turmeric. This anti-genotoxic effect was proportional to the concentrations applied. The results obtained, both in single and combined treatments indicate the suitability of the wing spot test for miming the normal intake of substances.
Article
Genotoxicity of 3-amino-1-methyl-5H-pyrido [4,3-b indole(Trp-P-2) on Drosophila was suppressed by chlorophyll. Using the wing hair spot test, we found that the formation of mutant hairs in adult files as a result of feeding them with Trp-P-2 in their larval stage was efficiently inhibited by coadininistration of chlorophyll. The decrease in the spot frequencies was dependent on the dose of chlorophyll, and at the highest dose used, where the ratio in weight of Trp-P-2 to chlorophyll was 1:80, a complete prevention of the small single-spot formation was observed. A similar inhibitory effect was detected for chlorophyllin, the chromophore of chlorophyll. In the studies to investigate the mechanism of inhibition, we observed that the mutagenicity of 3-hydroxyamino-1-methyl-5H-[4,3-bpyrido [Trp-P-2(NHOH)], the metabolically activated form of Trp-P-2, in Salmonella typhimurium TA98 was suppressed effectively with chlorophyll and chlorophyllin. We also found that chlorophyll and chlorophyllin can produce complexes with Trp-P-2 and Trp-P-2(NHOH). A straightforward mechanism of these inhibitions is that Trp-P-2 [and Trp-P-2(NHOH)] becomes no longer available to organisms on forming the chlorophyll complex.
Article
In Drosophila melanogaster new tester strains for the somatic mutation and recombination test (SMART) in the wing were constructed with the aim of increasing the metabolic capacity to activate promutagens. Some aspects of the genetic control of the xenobiotics metabolism in Drosophila are already known. In the DDT-resistant strain Oregon R(R) the RI gene at position 65.0 on chromosome 2 is responsible for the high constitutive expression of cytochrome P-450-dependent activities typical for this strain. Therefore, chromosomes 1 and 2 in the original mwh (multiple wing hairs) and flr3 (flare3) tester strains were substituted for chromosomes 1 and 2 from the Oregon R(R) strain. In assays with the model promutagen diethylnitrosamine an increased sensitivity of about 2.5-fold was found for this new set of 'HB' strains ('High Bioactivation (HB) cross').
Article
Dietary inhibitors of mutagenesis and carcinogenesis are of particular interest because they may be useful for human cancer prevention. Several mutagenesis inhibitors have been demonstrated to be carcinogenesis inhibitors also, e.g., ellagic acid, palmitoleic acid, and N-acetylcysteine. This means that the search for mutagenesis inhibitors may be useful for discovering anticarcinogenic agents. Many mutagenesis inhibitors have been discovered by the use of short-term assays, particularly the Ames Salmonella test. This simple in vitro system has provided opportunities to elucidate the mechanisms of inhibition. The elucidation of the mechanism may allow us to infer the possible anticarcinogenic activity of the reagent. In this chapter, inhibitors of mutagenesis and carcinogenesis that can arise as components of diet have been reviewed. Most of the inhibitors have been demonstrated to be effective against a specific class of mutagens or carcinogens. Therefore, it may be argued that these inhibitors are antagonistic only to those particular agents. Here again, understanding of the mechanisms of these inhibitions is necessary for the assessment. Dietary inhibitors reviewed in this article include: (1) as inhibitors of mutagenesis: porphyllins, fatty acids, vitamins, polyphenols, and sulfhydryl compounds, (2) as inhibitors of carcinogenesis: vitamins A, E and C, ellagic acid, sulfhydryl compounds, fats, selenium, calcium, and fiber. Further studies in this area of science appear to help establish the recipe of a healthy diet.
Article
Two alternative hypotheses are used to distinguish among the possibilities of a positive, inconclusive, or negative result in Drosophila mutagenicity tests. In the null hypothesis one assumes that there is no difference in the mutation frequency between control and treated series. The alternative hypothesis postulates a priori that the treatment results in an increased mutation frequency that is m times the spontaneous frequency. To test against the hypotheses, the conditional binomial test according to Kastenbaum and Bowman or the chi 2 test for proportions may be applied. These 2 methods are in principle equivalent. An alternative method which is based on determining confidence limits of observed mutation frequencies also leads to the same conclusions. The practical calculations are formulated and an application is shown with a test example demonstrating the genotoxicity of the pyrrolizidine alkaloid 7-acetylintermedine in the somatic wing mosaic test. In the Appendix, the calculus for the 3 testing methods is explained with a numerical example.
Article
A novel test system for the detection of mutagenic and recombinogenic activity of chemicals is described in detail. Drosophila melanogaster larvae trans-heterozygous for the mutations multiple wing hairs (mwh) and flare (flr) are exposed to the test compounds for various periods of time ranging from 96 hr to 1 hr. Induced mutations are detected as single mosaic spots on the wing blade of surviving adults that show either the multiple wing hairs or flare phenotype. Induced recombination leads to mwh and flr twin spots and also to a certain extent, to mwh single spots. Recording of the frequency and the size of the different spots allows for a quantitative determination of the mutagenic and recombinogenic effects. This and earlier studies with a small set of well-known mutagens indicate that the test detects monofunctional and polyfunctional alkylating agents (ethyl methanesulfonate, diepoxybutane, mitomycin C, Trenimon), mutagens forming large adducts (aflatoxin B1), DNA breaking agents (bleomycin), intercalating agents (5-aminoacridine, ICR-170), spindle poisons (vinblastine), and antimetabolites (methotrexate). In addition, the test detects mutagens unstable in aqueous solution (beta-propiolactone), gaseous mutagens (1,2-dibromoethane), as well as promutagens needing various pathways of metabolic activation (aflatoxin B1, diethylnitrosamine, dimethylnitrosamine, mitomycin C, and procarbazine). The rapidity and ease of performance as well as the low costs of the test necessitate a high priority for validation of this promising Drosophila short-term test.
Article
It has been suggested that the use of antimutagens and anticarcinogens in everyday life will be the most effective procedure for preventing human cancer and genetic disease. There are several ways in which mutagenesis can be reduced or prevented. Chemicals which act to interfere with DNA repair or with mutagen metabolism can be effective antimutagens: however such compounds may also increase the probability of mutations by different chemicals or at different sites. In contrast, mutagen scavengers may be less prone to increase mutations by other chemicals. Selected examples illustrate that antimutagenic effects are often specific to certain classes of mutagen and/or certain test systems. Thus, if antimutagens are to have any impact on human disease, it is essential that they are specifically directed against the most common mutagens in daily life. On our current understanding, these are quite diverse in nature, so that combinations of antimutagens will probably be necessary.
Article
The relationship between the induction of mutant clones and the time of mutagen treatment was studied in the somatic mutation and recombination test (SMART) in wing cells of Drosophila melanogaster. Larvae trans-heterozygous for the recessive marker mutations multiple wing hairs (mwh) and flare (flr) were produced. Batches of these larvae were then treated with mutagen at different ages spanning all three larval instars. Methyl methanesulfonate was fed acutely for 2 h by immersing the larvae in a solution of the mutagen mixed with powdered cellulose. Wings of the surviving adult flies were mounted and scored for the presence of spots. The frequency and size of single and twin spots were recorded separately. Twin spots are produced exclusively by mitotic recombination, whereas single spots can result from various types of mutational and exchange events. There exists a clear correlation between time of induction and frequency as well as size of the single spots. In young larvae only few but very large spots are induced, whereas in older larvae the frequencies are considerably increased but the sizes are smaller. The twin spots show a different relationship. Practically no twin spots are found in very young and in very old larvae. The results demonstrate that in the wing spot test the optimal age of the larvae for mutagen treatment is 72 h.
Article
In genetic toxicology it is important to know whether chemicals should be regarded as clearly hazardous or whether they can be considered sufficiently safe, which latter would be the case from the genotoxicologist's view if their genotoxic effects are nil or at least significantly below a predefined minimal effect level. A previously presented statistical decision procedure which allows one to make precisely this distinction is now extended to the question of how optimal experimental sample size can be determined in advance for genotoxicity experiments using the somatic mutation and recombination tests (SMART) of Drosophila. Optimally, the statistical tests should have high power to minimise the chance for statistically inconclusive results. Based on the normal test, the statistical principles are explained, and in an application to the wing spot assay, it is shown how the practitioner can proceed to optimise sample size to achieve numerically satisfactory conditions for statistical testing. The somatic genotoxicity assays of Drosophila are in principle based on somatic spots (mutant clones) that are recovered in variable numbers on individual flies. The underlying frequency distributions are expected to be of the Poisson type. However, some care seems indicated with respect to this latter assumption, because pooling of data over individuals, sexes, and experiments, for sample, can (but need not) lead to data which are overdispersed, i.e., the data may show more variability than theoretically expected. It is an undesired effect of overdispersion that in comparisons of pooled totals it can lead to statistical testing which is too liberal, because overall it yields too many seemingly significant results. If individual variability considered alone is not in contradiction with Poisson expectation, however, experimental planning can help to minimise the undesired effects of overdispersion on statistical testing of pooled totals. The rule for the practice is to avoid disproportionate sampling. It is recalled that for optimal power in statistical testing, it is preferable to use equal total numbers of flies in the control and treated series. Statistical tests which are based on Poisson expectations are too liberal if there is overdispersion in the data due to excess individual variability. In this case we propose to use the U test as a non-parametric two-sample test and to adjust the estimated optimal sample size according to (i) the overdispersion observed in a large historical control and (ii) the relative efficiency of the U test in comparison to the t test and related parametric tests.
Article
The somatic mutation and recombination test (SMART) in Drosophila melanogaster was carried out to investigate whether or not coffee can modulate the genotoxicity of the well-established mutagenic/carcinogenic chemicals cyclophosphamide (CPH), diethylnitrosamine (DEN), mitomycin C (MMC), procarbazine (PRO) and urethane (URE). For this purpose, 3-day-old larvae, trans-heterozygous for the wing hair markers mwh (multiple wing hairs) and flr3 (flare3), were raised on instant medium containing either the genotoxin alone or in combination with instant coffee. From the results obtained, it was evident that the chronic co-administration of coffee was effective in significantly reducing the frequencies of single and twin spots induced by CPH, DEN, MMC and URE but not PRO. The maximum reduction was observed in the frequencies of twin spots (produced by mitotic recombination) after feeding larvae on medium containing coffee in combination with the compounds CPH or URE.
Article
It has become increasingly clear that mutagenesis plays a central role in the multiple steps of carcinogenesis (42,51,155). Finding inhibitors in the diet and studying the mechanisms of their actions are important in providing humans a preventive measure against cancer (170). Mutagenesis- and carcinogenesis-inhibitors have been extensively studied, although the mechanisms of the inhibitions are, in many cases, not well understood.
Article
The protective effects of coffee against somatic mutation and mitotic recombination induced by cyclophosphamide (CPH), mitomycin C (MMC) and urethane (URE) were evaluated in the standard (ST) and high bioactivation (HB) crosses of the wing spot test in Drosophila melanogaster. These two crosses are characterized by different constitutive levels of cytochrome )-450-dependent enzyme activities. 3-day old larvae transheterozygous for the wing cell markers mwh (multiple wing hairs) and flr3 (flare3) were fed until pupation on medium containing a genotoxin alone or its combination with different concentrations of instant coffee. subsequently, the wings of the resulting adult flies were analysed for detecting single spots (mwh or flr3) originating from mutational or recombinational events as well as twin spots (mwh and flr3) originating exclusively from recombination. The results showed high sensitivity of the HB cross to URE. Co-administration of instant coffee was effective in exerting significant dose-related inhibitory effects on the genotoxicity of URE in the ST and the genetically susceptible HB cross. Similarly, coffee showed significant dose-related inhibitory effects on the genotoxicity of MMC in both crosses. The same protective effect was also observed with one concentration of coffee in combination with CPH. Pretreatment of 2-day-old HB larvae with coffee for 24 hr followed by treatment with URE was also effective in significantly reducing the induction of mutation and recombination. The magnitude of the protective effects of coffee against these three genotoxins was independent of the genotype of the larvae used for treatment, that is it was independent of the bioactivation capacity of these larvae. The study demonstrates the suitability of this assay for obtaining qualitative and quantitative data on the result of interactions among a genotoxin, an inhibitor of genotoxicity and bioactivation capacity of the host.
Article
Dietary components express a wide range of activities that can affect carcinogenesis. Naturally occurring substances in foods have been shown in laboratory experiments to serve as dietary antimutagens, either as bioantimutagens or as desmutagens. Dietary desmutagens may function as chemical inactivaters, enzymatic inducers, scavengers, or antioxidants. Dietary components may also act later in the carcinogenic process as tumor growth suppressors. Examples of dietary factors acting in each of these stages of carcinogenesis are presented, and potential anticarcinogens such as the carotenoids, tocopherols, phenolic compounds, glucosinolates, metal-binding proteins, phytoestrogens, and conjugated linoleic acid are discussed. Individual foods typically contain multiple potential anticarcinogens. Many of these substances can influence carcinogenesis through more than one mechanism. Some substances exhibit both anticarcinogenic and carcinogenic activity in vitro, depending on conditions. Epidemiologic research indicates that high fruit and vegetable consumption is associated with lower cancer risk. Little research has focused on the effects of single substances or single foods in man. Realization of the potential of foodborne substances to reduce the human burden of cancer will only be achieved with better measurement of dietary exposures and funding of multidisciplinary research in this area commensurate with its importance.
Article
The fruit fly Drosophila melangaster with its well developed array of genotoxicity test systems has been used in a number of studies on antigenotoxicity of various compounds and mixtures. In recent years, the newly developed Somatic Mutation and Recombination Tests (SMART) have mainly been employed. These one-generation tests make use of the wing or eye imaginal disc cells in larvae and have proven to be very efficient and sensitive. They are based on the principle that the loss of heterozygosity of suitable recessive markers can lead to the formation of mutant clones of cells that are then expressed as spots on the wings or eyes of the adult flies. We have employed the wing spot test with the two markers multiple wing hairs (mwh,3-0.3) and flare (flr,3-38.8). Three-day-old larvae, trans-heterozygous for these markers, are treated chronically or acutely by oral administration with the test compound(s) or complex mixtures. For antigenotoxicity studies, chronic co-treatments can be used, as well as separate pre-treatments with an antigenotoxic agent followed by a chronic treatment with a genotoxin. After eclosion, the wings of the adult flies are scored for the presence of single and twin spots. These spots can be due to different genotoxic events: either mitotic recombination or mutation (deletion, point mutation, specific types of translocation, etc.). The analysis of two different genotypes (one with structurally normal chromosomes, one with a multiply inverted balancer chromosome) allows for a quantitative determination of the recombinagenic activity of genotoxins. Results of two separate studies presented: (1) instant coffee has antirecombinagenic but not antimutagenic activity in the wing spot test; and (2) ascorbic acid and catechin are able to protect against in vivo nitrosation products of methyl urea in combination with sodium nitrite.
Article
Herbs have been used as food and for medicinal purposes for centuries. Research interest has focused on various herbs that possess hypolipidemic, antiplatelet, antitumor, or immune-stimulating properties that may be useful adjuncts in helping reduce the risk of cardiovascular disease and cancer. In different herbs, a wide variety of active phytochemicals, including the flavonoids, terpenoids, lignans, sulfides, polyphenolics, carotenoids, coumarins, saponins, plant sterols, curcumins, and phthalides have been identified. Several of these phytochemicals either inhibit nitrosation or the formation of DNA adducts or stimulate the activity of protective enzymes such as the Phase II enzyme glutathione transferase (EC 2.5.1.18). Research has centered around the biochemical activity of the Allium sp. and the Labiatae, Umbelliferae, and Zingiberaceae families, as well as flaxseed, licorice root, and green tea. Many of these herbs contain potent antioxidant compounds that provide significant protection against chronic diseases. These compounds may protect LDL cholesterol from oxidation, inhibit cyclooxygenase and lipoxygenase enzymes, inhibit lipid peroxidation, or have antiviral or antitumor activity. The volatile essential oils of commonly used culinary herbs, spices, and herbal teas inhibit mevalonate synthesis and thereby suppress cholesterol synthesis and tumor growth.