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ABSTRACT: This study was designed to develop a rodent model of hydrochlorothiazide (HCTZ) toxicity by associating its intake with a high-fat (HF) diet. Rats were fed for 16 weeks with a control diet or with an HF diet supplemented or not with different doses of HCTZ. HCTZ, in a similar way to the HF diet, caused a significant increase in fructosamine levels. HCTZ and HF diet intake caused a significant reduction in magnesium and potassium levels, as well as an increase in lipid peroxidation and vitamin C in liver. Importantly, negative correlations were found between magnesium and glucose levels as well as between magnesium and fructosamine levels. The association between HCTZ and the HF diet caused additional worsening of biochemical parameters related to glucose homeostasis, and further increased hepatic oxidative stress. Our results suggest that chronic intake of HCTZ or an HF diet causes metabolic changes that are consistent with the development of insulin resistance. In addition, the association of an HF diet and HCTZ treatment can exacerbate some of these biochemical alterations, suggesting that this model might be useful for studying HCTZ metabolic toxicity.
Magnesium research: official organ of the International Society for the Development of Research on Magnesium 05/2013; · 1.52 Impact Factor
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ABSTRACT: In this study, we investigated the potential protective effects of Valeriana officinalis (V. officinalis) against the toxicity induced by rotenone in Drosophila melanogaster (D. melanogaster). Adult wild-type flies were concomitantly exposed to rotenone (500μM) and V. officinalis aqueous extract (10mg/mL) in the food during 7 days. Rotenone-fed flies had a worse performance in the negative geotaxis assay (i.e. climbing capability) and open-field test (i.e. mobility time) as well as a higher incidence of mortality when compared to control group. V. officinalis treatment offered protection against these detrimental effects of rotenone. In contrast, the decreased number of crossings observed in the flies exposed to rotenone was not modified by V. officinalis. Rotenone toxicity was also associated with a marked decrease on the total-thiol content in the homogenates and cell viability of flies, which were reduced by V. officinalis treatment. Indeed, rotenone exposure caused a significant increase in the mRNA expression of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) and also in the tyrosine hydroxylase gene (TH). The expression of SOD and CAT mRNAs were normalized by V. officinalis treatment. Our results suggest that V. officinalis extract was effective in reducing the toxicity induced by rotenone in D. melonogaster as well as confirm the utility of this model to investigate potential therapeutic strategies on movement disorders, including Parkinson disease (PD).
NeuroToxicology 04/2013; · 3.10 Impact Factor
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ABSTRACT: It has been reported that oxidized LDLs (oxLDL) are involved in the pathogenesis of atherosclerosis, and that macrophages as well as other cells of the arterial wall can oxidize LDL in vitro, depending on the balance between intracellular prooxidant generation and antioxidant defense efficiency. Because of their potencial beneficial role in preventing atherosclerosis and other oxidative stress-related diseases, organoselenium compounds such as diphenyl diselenide (PhSe)2, are receiving increased attention. In the present work, we investigated the mechanisms underlying the protective effect exerted by (PhSe)2 on oxLDL-mediated effects in murine J774 macrophage-like cells. (PhSe)2 pretreatment reduced atherogenic signaling triggered by oxLDL in macrophages in vitro, namely: ROS generation, disturbance of (•)NO homeostasis, activation of matrix metalloproteinase, foam cell formation, and mitochondrial dysfunction. Moreover, the redox signaling effects of (PhSe)2 presented herein were accompanied by a downregulation of NF-κB-binding activity. The relatively strong performance of (PhSe)2 makes it an ideal candidate for further, expanded trials as a new generation of antioxidants for preventing atherosclerotic lesion.
Biochimie 04/2013; · 3.02 Impact Factor
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ABSTRACT: Organochalcogens, such as organoselenium and organotellurium compounds, can be neurotoxic to rodents. Since mitochondrial dysfunction plays a pivotal role in neurological disorders, the present study was designed to test the hypothesis that rat brain mitochondrial complexes (I, II, I-III, II-III and IV) could be molecular targets of organochalcogens. The results show that organochalcogens caused statistically significant inhibition of mitochondrial complex I activity, which was prevented by preincubation with NADH and fully blunted by reduced glutathione (GSH). Mitochondrial complex II activity remained unchanged in response to (PhSe)(2) treatment. Ebs and (PhTe)(2) caused a significant concentration-dependent inhibition of complex II that was also blunted by GSH. Mitochondrial complex IV activity was not modified by organochalcogens. Collectively, Ebs, (PhSe)(2) and (PhTe)(2) were more effective inhibitors of brain mitochondrial complex I than of complex II, whereas they did not affect complex IV. These observations are consistent with organochalcogens inducing mitochondrial complex I and II inhibition via their thiol-oxidase-like activity, with Ebs, (PhSe)(2) and (PhTe)(2) effectively oxidising critical thiol groups of these complexes.
Neurotoxicity Research 12/2012; · 3.51 Impact Factor
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Jean Paul Kamdem,
Sílvio Terra Stefanello,
Aline Augusti Boligon,
Caroline Wagner,
Ige Joseph Kade,
Romaiana Picada Pereira,
Alessandro De Souza Preste,
Daniel Henrique Roos,
Emily Pansera Waczuk,
Andre Storti Appel,
Margareth Linde Athayde,
Diogo Onofre Souza, João Batista Teixeira Rocha
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ABSTRACT: Antioxidant activity of the ethanolic extract and fractions from the stem bark of T. catigua was investigated. IC50 (for DPPH scavenging) by T. catigua varied from 9.17 ± 0.63 to 76.42 ± 5.87 mg mL-1 and total phenolic content varied from 345.63 ± 41.08 to 601.27 ± 42.59 mg GAE g-1 of dry extract. Fe2+-induced lipid peroxidation was significantly reduced by the ethanolic extract and fractions. Mitochondrial Ca2+-induced dichlorofluorescein oxidation was significantly reduced by the ethanolic extract in a concentration-dependent manner. Ethanolic extract reduced mitochondrial Dym only at high concentrations (40-100 mg mL-1), which indicates that its toxicity does not overlap with its antioxidant effects. Results suggest involvement of antioxidant activities of T. catigua in its pharmacological properties.
Acta Pharmaceutica 09/2012; 62(3):371-82. · 0.91 Impact Factor
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ABSTRACT: Valeriana officinalis L. (Valerian) is widely used as a traditional medicine to improve the quality of sleep. Although V. officinalis have been well documented as promising pharmacological agent; the exact mechanisms by which this plant act is still unknown.
Limited literature data have indicated that V. officinalis extracts can exhibit antioxidant properties against iron in hippocampal neurons in vitro. However, there is no data available
about the possible antioxidant effect of V. officinalis against other pro-oxidants in brain. In the present study, the protective effect of V. officinalis on lipid peroxidation (LPO) induced by different pro-oxidant agents with neuropathological importance was examined. Ethanolic
extract of valerian (0–60μg/ml) was tested against quinolinic acid (QA); 3-nitropropionic acid; sodium nitroprusside; iron
sulfate (FeSO4) and Fe2+/EDTA induced LPO in rat brain homogenates. The effect of V. officinalis in deoxyribose degradation and reactive oxygen species (ROS) production was also investigated. In brain homogenates, V. officinalis inhibited thiobarbituric acid reactive substances induced by all pro-oxidants tested in a concentration dependent manner.
Similarly, V. officinalis caused a significant decrease on the LPO in cerebral cortex and in deoxyribose degradation. QA-induced ROS production in
cortical slices was also significantly reduced by V. officinalis. Our results suggest that V. officinalis extract was effective in modulating LPO induced by different pro-oxidant agents. These data may imply that V. officinalis extract, functioning as antioxidant agent, can be beneficial for reducing insomnia complications linked to oxidative stress.
Neurochemical Research 04/2012; 34(8):1372-1379. · 2.24 Impact Factor
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Romaiana Picada Pereira,
Roselei Fachinetto,
Alessandro de Souza Prestes,
Robson Luiz Puntel,
Gloria Narjara Santos da Silva,
Berta Maria Heinzmann,
Ticiane Krapf Boschetti,
Margareth Linde Athayde,
Marilise Escobar Bürger,
Ademir Farias Morel,
Vera Maria Morsch, João Batista Teixeira Rocha
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ABSTRACT: Considering the important role of oxidative stress in the pathogenesis of several neurological diseases, and the growing evidence
of the presence of compounds with antioxidant properties in the plant extracts, the aim of the present study was to investigate
the antioxidant capacity of three plants used in Brazil to treat neurological disorders: Melissa officinalis, Matricaria recutita and Cymbopogon citratus. The antioxidant effect of phenolic compounds commonly found in plant extracts, namely, quercetin, gallic acid, quercitrin
and rutin was also examined for comparative purposes. Cerebral lipid peroxidation (assessed by TBARS) was induced by iron
sulfate (10μM), sodium nitroprusside (5μM) or 3-nitropropionic acid (2mM). Free radical scavenger properties and the chemical
composition of plant extracts were assessed by 1′-1′ Diphenyl-2′ picrylhydrazyl (DPPH) method and by Thin Layer Chromatography
(TLC), respectively. M. officinalis aqueous extract caused the highest decrease in TBARS production induced by all tested pro-oxidants. In the DPPH assay, M. officinalis presented also the best antioxidant effect, but, in this case, the antioxidant potencies were similar for the aqueous, methanolic
and ethanolic extracts. Among the purified compounds, quercetin had the highest antioxidant activity followed by gallic acid,
quercitrin and rutin. In this work, we have demonstrated that the plant extracts could protect against oxidative damage induced
by various pro-oxidant agents that induce lipid peroxidation by different process. Thus, plant extracts could inhibit the
generation of early chemical reactive species that subsequently initiate lipid peroxidation or, alternatively, they could
block a common final pathway in the process of polyunsaturated fatty acids peroxidation. Our study indicates that M. officinalis could be considered an effective agent in the prevention of various neurological diseases associated with oxidative stress.
Neurochemical Research 04/2012; 34(5):973-983. · 2.24 Impact Factor
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ABSTRACT: The effect of dietary diphenyl diselenide (1ppm) on N-nitroso-N-methylurea (NMU)-induced mammary carcinogenesis was examined in female Wistar rats. Beginning at 5weeks of age, the animals
were fed with either control or diphenyl-diselenide-supplied diets until the end of the study (210days). At 50days of age,
mammary tumor was induced by the administration of three doses of NMU (50mg/kg body wt, intraperitoneally) once a week for
3weeks. In experimental trials, latency to tumor onset was extended in rats fed with diet supplemented with diphenyl diselenide
(P<0.05). The incidence and frequency of tumors were significantly small in animals supplemented with diphenyl diselenide.
However, the multiplicity of tumors was not altered by dietary diphenyl diselenide. Diphenyl diselenide supplementation also
restored superoxide dismutase (SOD) activity and vitamin C levels altered in the NMU group (P<0.05). Our results suggest that diphenyl diselenide can be considered a chemopreventive agent, even when supplemented at
a relatively low concentration.
Archive für Toxikologie 04/2012; 82(9):655-663. · 4.67 Impact Factor
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ABSTRACT: Acetaminophen (APAP) hepatotoxicity has been related to several cases of hepatitis, cirrhosis, and hepatic transplant. As APAP hepatotoxicity is related to reactive oxygen species (ROS) formation and excessive oxidative stress, natural antioxidant compounds have been tested as an alternative therapy to diminish the hepatic dysfunction induced by APAP. Taraxacum officinale Weber (Family Asteraceae), commonly known as dandelion, is used for medicinal purposes because of its choleretic, diuretic, antioxidant, anti-inflammatory, and hepatoprotective properties. This study evaluated the hepatoprotective activity of T. officinale leaf extract against APAP-induced hepatotoxicity. T. officinale was able to decrease thiobarbituric acid-reactive substance levels induced by 200 mg/kg APAP (p.o.), as well as prevent the decrease in sulfhydryl levels caused by APAP treatment. Furthermore, histopathological alterations, as well as the increased levels of serum aspartate and alanine aminotransferases caused by APAP, were prevented by T. officinale (0.1 and 0.5 mg/mL). In addition, T. officinale extract also demonstrated antioxidant activity in vitro, as well as scavenger activity against 2,2-diphenyl-1-picrylhydrazyl and nitric oxide radicals. Our results clearly demonstrate the hepatoprotective effect of T. officinale against the toxicity induced by APAP. The possible mechanisms involved include its scavenger activities against ROS and reactive nitrogen species, which are attributed to the content of phenolic compounds in the extract.
Journal of medicinal food 03/2012; 15(6):549-56. · 1.39 Impact Factor
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ABSTRACT: The aim of the present study was to evaluate the potential pharmacological and toxicological properties of (E)-1-(1-(methylthio)-1-(selenopheny) hept-1-en-2-yl) pyrrolidin-2-one (compound 1), an organoselenium compound. In vitro experiments showed that compound 1 presented a reduction in the lipid peroxidation induced by Fe²⁺ in thiobarbituric acid-reactive species (TBARS) production, and in the generation of reactive species caused by Fe²⁺/malonate in DCFH-DA oxidation. The high dose (500 mg/kg) induced an increase on ALT but not on AST activity. Hepatic, but not cerebral, δ-ALA-D activity from mice treated with 500 mg/kg presented a significant inhibition. Brain catalase activity was significantly inhibited by 100 mg/kg whereas hepatic catalase activity showed a significant increase at all doses. Hepatic lipid peroxidation was diminished only at lowest dose (100 mg/kg) whereas for brain tissue, all doses induced a significant reduction in TBARS levels. Brain and liver ascorbic acid contents were increased only at highest dose of compound 1. Urea and creatinine levels were not significantly altered by treatments. This is a promising compound with antioxidant activity and low toxicity, suggesting the potential beneficial activity of compound 1 against oxidative damage in many parameters studied in rats and mice.
Cell Biology and Toxicology 03/2012; 28(4):213-23. · 2.51 Impact Factor
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ABSTRACT: Organochalcogens have been widely studied given their antioxidant activity, which confers neuroprotection, antiulcer, and antidiabetic properties. Given the complexity of mammalian models, understanding the cellular and molecular effects of organochalcogens has been hampered. The nematode worm Caenorhabditis elegans is an alternative experimental model that affords easy genetic manipulations, green fluorescent protein tagging, and in vivo live analysis of toxicity. We previously showed that manganese (Mn)-exposed worms exhibit oxidative-stress-induced neurodegeneration and life-span reduction. Here we use Mn-exposed worms as a model for an oxidatively challenged organism to investigate the underlying mechanisms of organochalcogen antioxidant properties. First, we recapitulate in C. elegans the effects of organochalcogens formerly observed in mice, including their antioxidant activity. This is followed by studies on the ability of these compounds to afford protection against Mn-induced toxicity. Diethyl-2-phenyl-2-tellurophenyl vinyl phosphonate (DPTVP) was the most efficacious compound, fully reversing the Mn-induced reduction in survival and life span. Ebselen was also effective, reversing the Mn-induced reduction in survival and life span, but to a lesser extent compared with DPTVP. DPTVP also lowered Mn-induced increases in oxidant levels, indicating that the increased survival associated with exposure to this compound is secondary to a decrease in oxidative stress. Furthermore, DPTVP induced nuclear translocation of the transcriptional factor DAF-16/FOXO, which regulates stress responsiveness and aging in worms. Our findings establish that the organochalcogens DPTVP and ebselen act as antiaging agents in a model of Mn-induced toxicity and aging by regulating DAF-16/FOXO signaling and attenuating oxidative stress.
Free radical biology & medicine 03/2012; 52(9):1903-10. · 5.42 Impact Factor
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Guilherme Pires Amaral,
Gustavo Orione Puntel,
Cristiane Lenz Dalla Corte,
Fernando Dobrachinski,
Rômulo Pillon Barcelos,
Luiza Lena Bastos,
Daiana Silva Avila, João Batista Teixeira Rocha,
Edegar Ozorio da Silva,
Robson Luiz Puntel,
Félix Alexandre Antunes Soares
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ABSTRACT: Oxidative stress is involved in the etiology of several chronic diseases, including cardiovascular disease, diabetes, cancer, and neurodegenerative disorders. From this perspective, we have evaluated the possible antioxidant capacities of five different phthalocyanines (PCs), consisting of four metallophthalocyanines (MPCs) and one simple phthalocyanine (PC) in order to explore, for the first time, the potential antioxidant activities of these compounds. Our results show that all PCs tested in this study have significant antioxidant activity in lipid peroxidation assay, providing protection from sodium nitroprusside -induced oxidative damage to supernatant from the homogenized liver, brain, e rim of mice. Compared to the non-induced control, the PCs were generally more efficient in reducing malondialdehyde levels in all assays on lipid peroxidation induced by sodium nitroprusside; the order of approximate decrease in efficiency was as follows: manganese-PC (better efficiency)>copper-PC>iron-PC>zinc-PC>PC (worst efficiency). Furthermore, the copper-PC and manganese-PC compounds exerted a significant protective effect in deoxyribose degradation assays, when employing Fe(2+), Fe(2+)+H(2)O(2), and H(2)O(2) solutions. In conclusion, all PCs tested here were shown to be promising compounds for future in vivo investigations, because of their potential antioxidant activities in vitro.
Toxicology in Vitro 02/2012; 26(1):125-32. · 2.78 Impact Factor
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ABSTRACT: Manganese (Mn) is an essential element for biological systems; however occupational exposure to high levels of this metal may lead to neurodegenerative disorders, resembling Parkinson's disease (PD). While its mechanisms of neurotoxicity have yet to be fully understood, oxidative stress plays a critical role. Thus, the main goal of this study was to investigate the efficacy of aqueous extract of Melissa officinalis in attenuating Mn-induced brain oxidative stress in mice. Sixteen male mice were randomly divided into two groups and treated for 3 months: the first group consumed tap water (control group) and the second group was treated with Mn (50 mg/kg/day for habituation during the first 15 days followed by 100 mg/kg/day for additional 75 days) in the drinking water. After 3 months both groups were sub divided (n=4 per group) and treated for additional 3 months with Mn and/or M. officinalis in the drinking water. The first group (control) was treated with water and served as control; the second group (M. officinalis) was treated with M. officinalis (100 mg/kg/day); the third group was treated with Mn (100 mg/kg/day); the fourth group (Mn+M. officinalis) was treated with both Mn and M. officinalis (100 mg/kg/day each). Mn-treated mice showed a significant increase in thiobarbituric acid reactive species (TBARS) levels (a marker of oxidative stress) in both the hippocampus and striatum. These changes were accompanied by a decrease in total thiol content in the hippocampus and a significant increase in antioxidant enzyme activity (superoxide dismutase and catalase) in the hippocampus, striatum, cortex and cerebellum. Co-treatment with M. officinalis aqueous extract in Mn-treated mice significantly inhibited the antioxidant enzyme activities and attenuated the oxidative damage (TBARS and decreased total thiol levels). These results establish that M. officinalis aqueous extract possesses potent antioxidative properties, validating its efficacy in attenuating Mn-induced oxidative stress in the mouse brain.
Brain research bulletin 01/2012; 87(1):74-9. · 2.18 Impact Factor
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ABSTRACT: Thioredoxin reductase (TrxR) isoforms play important roles in cell physiology, protecting cells against oxidative processes. In addition to its endogenous substrates (Trx isoforms), hepatic TrxR can reduce organic selenium compounds such as ebselen and diphenyl diselenide to their selenol intermediates, which can be involved in their hepatoprotective properties. Taking this into account, the aim of the present study was to evaluate the hypothesis that ebselen, diphenyl diselenide and its analogs (4,4'-bistrifluoromethyldiphenyl diselenide, 4,4'-bismethoxydiphenyl diselenide, 4.4'-biscarboxy-diphenyl diselenide, 4,4'-bischlorodiphenyl diselenide, 2,4,6,2',4',6'-hexamethyldiphenyl diselenide) could be substrates of rat brain TrxR. In the presence of partially purified rat brain TrxR, diphenyl diselenide, bismethoxydiphenyl diselenide and bischlorodiphenyl diselenide (at 10, 15 and 20μM) stimulated NADPH oxidation, indicating that they are substrates of brain TrxR. In contrast, ebselen and bistrifluoromethyldiphenyl diselenide, that have been previously demonstrated to be substrate of hepatic TrxR, were not reduced by rat brain TrxR. The results presented here suggest that diphenyl diselenide can exert neuroprotective effects by mimicking glutathione peroxidase activity and also via its reduction by TrxR. However, ebselen was not reduced by brain TrxR, indicating that the neuroprotective properties of this compound is possibly mediate by its glutathione peroxidase-like activity.
Neuroscience Letters 08/2011; 503(1):1-5. · 2.11 Impact Factor
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ABSTRACT: Acetaminophen (APAP) hepatotoxicity has been related with several cases of cirrhosis, hepatitis and suicides attempts. Notably, oxidative stress plays a central role in the hepatic damage caused by APAP and antioxidants have been tested as alternative treatment against APAP toxicity. In the present study, we observed the hepatoprotector activity of the diethyl-2-phenyl-2-tellurophenyl vinylphosphonate (DPTVP), an organotellurium compound with low toxicity and high antioxidant potential. When the dose of 200 mg/kg of APAP was used, we observed that all used doses of DPTVP were able to restore the -SH levels that were depleted by APAP. Furthermore, the increase in thiobarbituric acid reactive substances levels and in the seric alanine aminotransferase (ALT) activity and the histopathological alterations caused by APAP were restored to control levels by DPTVP (30, 50 and 100 μmol/kg). On the other hand, when the 300 mg/kg dose of APAP was used, DPTVP restored the non-proteic -SH levels and repaired the normal liver morphology of the intoxicated mice only at 50 μmol/kg. Our in vitro results point out to a scavenging activity of DPTVP against several reactive species, action that is attributed to its chemical structure. Taken together, our results demonstrate that the pharmacological action of DPTVP as a hepatoprotector is probably due to its scavenging activity related to its chemical structure.
European journal of pharmacology 07/2011; 661(1-3):92-101. · 2.59 Impact Factor
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ABSTRACT: Oral movements are associated with important neuropathologies as Parkinson's disease and tardive dyskinesia. However, until this time, there has been no known efficacious treatment, without side effects, for these disorders. Thus, the aim of the present study was to investigate the possible preventive effects of V. officinalis, a phytotherapic that has GABAergic and antioxidant properties, in vacuous chewing movements (VCMs) induced by reserpine in rats. Adult male rats were treated with reserpine (1 mg/kg, s.c.) and/or with V. officinalis (in the drinking water, starting 15 days before the administration of the reserpine). VCMs, locomotor activity and oxidative stress measurements were evaluated. Furthermore, we carried out the identification of valeric acid and gallic acid by HPLC in the V. officinalis tincture. Our findings demonstrated that reserpine caused a marked increase on VCMs and the co-treatment with V. officinalis was able to reduce the intensity of VCM. Reserpine did not induce oxidative stress in cerebral structures (cortex, hippocampus, striatum and substantia nigra). However, a significant positive correlation between DCF-oxidation (an estimation of oxidative stress) in the cortex and VCMs (p < 0.05) was observed. Moreover, a negative correlation between Na(+)K(+)-ATPase activity in substantia nigra and the number of VCMs was observed (p < 0.05). In conclusion, V. officinalis had behavioral protective effect against reserpine-induced VCMs in rats; however, the exact mechanisms that contributed to this effect have not been completely understood.
Acta Neurovegetativa 04/2011; 118(11):1547-57. · 2.73 Impact Factor
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11/2010: pages 357 - 385; , ISBN: 9780470917060
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Marcos Raniel Straliotto,
Gianni Mancini,
Jade de Oliveira,
Evelise Maria Nazari,
Yara Maria Rauh Müller,
Alcir Dafre,
Susana Ortiz,
Edson Luiz Silva,
Marcelo Farina,
Alexandra Latini, João Batista Teixeira Rocha,
Andreza Fabro de Bem
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ABSTRACT: The simple organoselenium compound diphenyl diselenide (PhSe)(2) is a promising new pharmacological agent. However, few toxicological evaluations of this molecule have been reported. We evaluated the effects of acute administration of (PhSe)(2) on toxicological parameters in rabbits. Adult New Zealand rabbits were exposed to (PhSe)(2) (5-500 micromol kg(-1) , intraperitoneally) once a day for 5 days. Exposure to 500 micromol kg(-1) caused 85% mortality. Exposure to 50 micromol kg(-1) of (PhSe)(2) increased the glutathione levels in the hippocampus, kidney, heart, muscle and blood, whereas lipoperoxidation (TBARS) decreased in the cerebellum and kidney after exposure to 5 micromol kg(-1) . The activity of glutathione peroxidase increased in the heart and muscle of rabbits treated with 50 micromol kg(-1) of (PhSe)(2) and glutathione reductase activity was reduced in the cerebellum, cerebral cortex and kidney. Treatment with (PhSe)(2) reduced the activity of δ-aminolevulinate dehydratase in the hippocampus and increased this activity in the heart, but did not alter the activity of complexes I and II of the respiratory chain in the liver and brain. Hepatic and renal biochemical and histological parameters were not modified by (PhSe)(2) and apoptosis was not detected in these tissues; however, the hepatic cells tended to accumulate fat vacuoles. These results indicated that acute toxicology to (PhSe)(2) in rabbit is dependent on the dose, which should motivate further experiments on the therapeutic properties of this compound.
Journal of Applied Toxicology 11/2010; 30(8):761-8. · 2.48 Impact Factor
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ABSTRACT: Selenium can counteract methylmercury (MeHg) neurotoxicity. However, data about the neuroprotective effects of sodium selenite (Na(2)SeO(3)) on the activity of mitochondrial complexes and creatine kinase (mtCK) are scarce. Therefore, this study investigated the effects of the chronic exposure to Na(2)SeO(3) on brain energy metabolism and oxidative stress parameters in MeHg-poisoned mice. Adult male mice were orally treated with MeHg (40 mg L(-1) in drinking water, ad libitum) during 21 days and simultaneously administrated with daily subcutaneous injections of Na(2)SeO(3) (5 μmol kg(-1)), a potential neuroprotectant. Mitochondrial complexes I to IV and mtCK activities were measured in cerebral cortex mitochondria. The cerebro-cortical tissue was also used to evaluate the antioxidant enzymes glutathione peroxidase (GPx) and glutathione reductase (GR) activities, as well as lipid peroxidation. Metal deposition was followed autometalographically (AMG). Na(2)SeO(3) partially prevented MeHg-induced inhibition of complexes II-III, IV and mtCK activities; however, it was unable to prevent MeHg-induced complex I and II inhibition. MeHg increased lipid peroxidation, GR activity and decreased GPx activity in the cerebral cortex; however, Na(2)SeO(3) did not modify such events. Furthermore, Na(2)SeO(3)per se inhibited complexes I, II-III and IV and mtCK activities and increased GPx and GR activities and lipid peroxidation. These data show that inorganic selenium was ineffective in preventing most of the MeHg-induced brain biochemical alterations. However, the most prominent finding was the selenium-induced reduction of cells labelled for metal deposition. Although, the literature supports the beneficial effects of selenium against mercury toxicity, the toxic effects elicited by Na(2)SeO(3), alone or in combination with mercury, should be considered when this compound is proposed as a potential protective therapy for MeHg poisoning.
International journal of developmental neuroscience: the official journal of the International Society for Developmental Neuroscience 11/2010; 28(7):631-7. · 2.03 Impact Factor
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ABSTRACT: Methylmercury (MeHg), a potent neurotoxicant, easily passes through the blood-brain barrier and accumulates in brain causing severe irreversible damage. However, the underlying neurotoxic mechanisms elicited by MeHg are still not completed defined. In this study, we aimed to investigate the in vitro toxic effects elicited by crescent concentrations (0-1500 microM) of MeHg on creatine kinase (CK) activity, thiol content (NPSH) and protein carbonyl content (PCC) in mouse brain preparations. In addition, CK activity, MTT reduction and DCFH-DA oxidation (reactive oxygen species (ROS) formation) were also measured in C6 glioma cell linage. CK activity was severely reduced by MeHg treatment in mouse brain preparations. This inhibitory effect was positively correlated to the MeHg-induced reduction of NPSH levels and increment in PCC. Moreover, the positive correlation between brain CK activity and NPSH levels was observed at either 15 or 60 min of MeHg pre-incubation. In addition, MeHg-treated C6 cells showed also a significant inhibition of CK activity at MeHg concentrations, as low as, 50 microM in parallel to reduced mitochondrial function and increased ROS production. Taking together, these data demonstrate that MeHg severely affects CK activity, an essential enzyme for brain energy buffering to maintain cellular energy homeostasis. This effect appears to be mediated by oxidation of thiol groups that might cause subsequent oxidative stress.
NeuroToxicology 09/2010; 31(5):454-60. · 3.10 Impact Factor
