Influence of orange juice over the genotoxicity induced by alkylating agents: An in vivo analysis

Curso de Nutrição, Departamento de Educação Física e Saúde, Universidade de Santa Cruz do Sul (UNISC), Santa Cruz do Sul, RS, Brazil.
Mutagenesis (Impact Factor: 2.79). 08/2005; 20(4):279-83. DOI: 10.1093/mutage/gei034
Source: PubMed


There is considerable epidemiological evidence indicating an association between diets rich in fresh fruit and vegetables and a decreased incidence of cancers. Methyl methanesulfonate (MMS) and cyclophosphamide (CP) are alkylating agents that differ in their mode of action. MMS is a directly-acting, monofunctional agent, while CP is a bifunctional agent that requires metabolic activation to a reactive metabolite. To evaluate if orange juice could reduce DNA damage induced by these alkylating agents, mice were treated orally (by gavage) with MMS and CP, prior to and after treatment with orange juice. DNA damage was evaluated by the comet assay in peripheral white blood cells. Under these experimental conditions, orange juice reduced the extent of DNA damage caused by both mutagens. For MMS, the antigenotoxic effect of the orange juice was both protective (orange juice pre-treatment) and reparative (orange juice post-treatment); for CP, the effect was reparative only. The components of orange juice can have several biological effects, including acting as targets of toxicants and modulating metabolization/detoxification routes. Considering the different mechanisms of the action of the two drugs, different protective effects are suggested. These results demonstated the ability of the in vivo comet assay to detect in vivo modulation of MMS and CP mutagenicity by orange juice.

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Available from: Daniel Prá, Oct 07, 2015
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    • "This study showed no significant increase in the levels of damage to genetic material in the blood cells of mice treated orally with the infusion of this plant used at different concentrations and for different exposure times, compared with the saline group. Based on studies of plant phytochemicals, it is known that phenolic compounds, in general, can stimulate the DNA repair system, through transcriptional regulation of mRNA stabilisation (Franke et al., 2005). Coumarins also have antioxidant activity and are especially effective against the hydroxyl radical (Lo et al., 2004). "
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    ABSTRACT: Ethnobotanical studies have investigated the use of leaves of Cunila microcephala for respiratory, stomach and gastrointestinal disorders. The essential oil of this plant is mostly composed of menthofuran, which has a hepatotoxic effect. Due to the popular use of this plant in southern Brazil, this study aimed to perform phytochemical profile of C. microcephala to detect and determine the amount of secondary metabolites and to evaluate their microbiological activity in vitro and genetic damage in vivo, indicative of genotoxicity, to ensure safe use of the plant. The leaf extract of C. microcephala was investigated for the presence of phenolic compounds, such as tannins, coumarins and flavonoids. This extract contained 193.23 mg/ml of phenolic compounds. In our in vitro analysis of microbiological activity, the crude leaf extract of C. microcephala showed 6 mm zone of inhibition against Staphylococcus aureus; fractions of dichloromethane and ethyl acetate showed 4 mm zones. In the genotoxic analysis, using the comet assay, no genotoxic effects were observed in blood samples and the liver at 125, 250 and 500 mg/kg. According to the results, C. microcephala presents interesting secondary compounds with biological activity, showing antimicrobial effects in vitro and no genotoxic effects in vivo.
    Journal of medicinal plant research 06/2014; 8(21):780-787. DOI:10.5897/JMPR2014.5428 · 0.88 Impact Factor
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    • "The main finding of this work has been to demonstrate the protection obtained by the juice from a variety of prickly pear fruit frequently consumed in México against damage caused by methyl methanesulfonate, which is an alkylating agent that has demonstrated its mutagenic, carcinogenic and teratogenic abilities in different trials [43]. In general, the toxic mechanism of action involves the direct alkylation by type 2 nucleophilic substitution of guanine and adenine, which results in their ability to induce single and double strand breaks, as well as to generate reactive oxygen species [33]. "
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    ABSTRACT: Plants belonging to the genus Opuntia spp. are the most abundant of the Cactaceae family, grown throughout America and the Mediterranean central area. Its fruit, known as cactus pear or prickly pear, is an oval berry grouped in different colors. Some studies have shown its antioxidant activities which may help in preventing chronic pathologies such as diabetes. The purpose of the study was to evaluate the antioxidant capacity of three varieties of prickly pear juice (red-purple, white-green and yellow-orange) in five different concentrations (100, 250, 500, 750, and 1000 mg/mL) by DPPH (1,1-diphenyl-2-picrylhydrazyl radical) colorimetric method, selecting the best variety to determine its anticlastogenic potential against methyl methanesulfonate (MMS). The results indicate that the highest antioxidant was found in the juice of the prickly pear red-purple variety (PPRP), in all concentrations. Its anticlastogenic potential was therefore evaluated with a micronucleus assay. The experiment was run over two weeks. A negative control was included along with a positive control with MMS (40 mg/kg), a group of mice treated with PPRP (25 mL/kg), and three groups with PPRP (in doses of 25, 16.5 and 8.3 mL/kg) plus the mutagen. The PPRP was administered daily by oral gavage and the MMS was injected intraperitoneally five days prior to the end of the experiment. Blood samples were obtained at 0, 24, 48, 72 and 96 h in order to determine the frequency of micronucleated polychromatic erythrocytes (MNPE). The results indicated that PPRP is not a genotoxic agent, on the contrary, it may reduce the number of MNPE. In this regard, the PPRP showed an anticlastogenic effect directly proportional to its concentrations. Thus, the highest protection was obtained with a concentration of 25 mL/kg after 48 h of treatment.
    Nutrients 10/2013; 5(10):4145-58. DOI:10.3390/nu5104145 · 3.27 Impact Factor
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    • "Recent scientific research has shown that many plants can induce genotoxicity and mutagenicity which are related to human disorders, such as cancer or degenerative diseases [4] [5] [6] [7] [8]. On the other hand, beneficial effects are also attributed to plants, including antimutagenicity, [9]chemoprotection, and antioxidant activity [10] [11] [12] [13]. Aesculus hippocastanum L. (AH), popularly known as " horse chestnut " , is a native European plant widely distributed all over the world. "
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    ABSTRACT: Aesculus hippocastanum L. (Sapindaceae), vulgarly known as horse chestnut, is a native European plant, but widely distributed all over the world. The parts used in medicine are the seeds and the bark of young branches. The seed extract has been marketed as a phytotherapeutic product and it is extensively recommended for treatment of chronic venous insufficiency, traumatic edema, hemorrhoid and postoperative edema. Most of the beneficial effects of horse chestnut are attributed to its principal component aescin. The present study aims to evaluate the citotoxic, genotoxic, mutagenic, and antioxidant activity of this seed extract by performing a set of bacterial and cell-free tests. Phytochemical screening and thin layer chromatography confirmed the presence of aescin as well as others chemical constituents in the studied extract. Negative results were obtained for the occurrence of double-strand breaks in pBCKS plasmid DNA. Two different effects were detected in Escherichia coli strains CC104 and CC104mutMmutY: mutagenic (non-oxidative lesions) and antioxidant. The mutagenic effect was confirmed by Kado assay, where the extract was considered weakly mutagenic towards frameshift mutations. Moreover, the extract demonstrated to protect bacterial cells from lesions induced by mitomycin C, suggesting an antioxidative potential. A. hippocastanum seed extract demonstrated to be genotoxic and weakly mutagenic, as well as antioxidative.
    Biomedicine and Preventive Nutrition 07/2013; 3(3):261–266. DOI:10.1016/j.bionut.2012.10.014
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