ascorbic-acid and methylmercuric-chloride

The present study was undertaken to evaluate methylmercury-induced alterations in hepatic enzymes and oxidative stress markers in liver tissue of rainbow trout (Oncorhynchus mykiss) by using a perfusion method, and to explore possible protective effect of vitamin C against these alterations. Forty-eight fish were divided into six groups containing control, test, and amelioration groups. The liver of fish in the test groups were exposed to different doses of methylmercury, i.e., 0.6, 1.2, and 2.4 μg L(-1), respectively, for 120 min. In the amelioration group, liver was treated with vitamin C (17.2 μg L(-1)) along with high dose (2.4 μg L(-1)) of methylmercury. The results of the present study showed that exposure with 0.6, 1.2, and 2.4 μg L(-1) of methylmercury significantly increased (p < 0.05) hepatic enzyme activities (alanine transaminase (ALT), aspartate transaminase (AST), and Lactate dehydrogenase (LDH)) and malondialdehyde (MDA) level, as a marker of lipid peroxidation. On the other hand, the concentration of reduced glutathione (GSH) and total antioxidant capacity of the liver decreased (p < 0.05) in the methylmercury-exposed groups when compared to the control group. Pearson's correlation analysis revealed a positive correlation between MDA concentration and ALT, AST, and LDH activities in the methylmercury groups, suggesting that the enhanced lipid peroxidation may be linked to hepatic damage caused by methylmercury. Treatment with vitamin C in methylmercury-exposed group led to a significant decrease (p < 0.05) in MDA concentration and hepatic enzyme activities and significant increase (p < 0.05) in levels of GSH and total antioxidant capacity. The values of measured parameters in the methylmercury + vitamin C group were comparable to those of the control group. The results of the present study demonstrated that methylmercury exposure induces oxidative stress in the liver of rainbow trout and treatment with vitamin C can protect fish liver against this oxidative insult.

Topics: Alanine Transaminase; Animals; Antioxidants; Ascorbic Acid; Aspartate Aminotransferases; Glutathione; Lipid Peroxidation; Liver; Malondialdehyde; Methylmercury Compounds; Oncorhynchus mykiss; Oxidative Stress

To evaluate the protector effect of ascorbic acid (AA) against anxiogenic-like effect induced by methylmercury (MeHg) exposure, adult zebrafish were treated with AA (2 mg g(-1), intraperitoneal [i.p.]) before MeHg administration (1.0 μg g(-1), i.p.). Groups were tested for the light/dark preference as a behavioral model of anxiety, and the content of serotonin and its oxidized metabolite tryptamine-4,5-dione (T-4,5-D) in the brain was determined by high-performance liquid chromatography. MeHg has produced a marked anxiogenic profile in both tests, and this effect was accompanied by a decrease in the extracellular levels of serotonin, and an increase in the extracellular levels of T-4,5-D. Added to this, a marked increase in the formation of a marker of oxidative stress accompanied these parameters. Interestingly, the anxiogenic-like effect and biochemical alterations induced by MeHg were blocked by pretreatment with AA. These results for the first time demonstrated the potential protector action of AA in neurobehavioral and neurochemical alterations induced by methylmecury exposure demonstrating that zebrafish model could be used as an important tool for testing substances with neuroprotector actions.

Topics: Animals; Antioxidants; Anxiety; Ascorbic Acid; Brain; Chromatography, High Pressure Liquid; Environmental Pollutants; Indolequinones; Methylmercury Compounds; Serotonin; Tryptamines; Zebrafish

Oxidative stress has been pointed out as an important molecular mechanism in methylmercury (MeHg) intoxication. At low doses, diphenyl diselenide ((PhSe)2), a structurally simple organoselenium compound, has been shown to possess antioxidant and neuroprotective properties. Here we have examined the possible in vivo protective effect of diphenyl diselenide against the potential pro-oxidative effects of MeHg in mouse liver, kidney, cerebrum and cerebellum. The effects of MeHg exposure (2 mg/(kg day) of methylmercury chloride 10 ml/kg, p.o.), as well as the possible antagonist effect of diphenyl diselenide (1 and 0.4 mg/(kg day); s.c.) on body weight gain and on hepatic, cerebellar, cerebral and renal levels of thiobarbituric acid reactive substances (TBARS), non-protein thiols (NPSH), ascorbic acid content, mercury concentrations and activities of antioxidant enzymes (glutathione peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD)) were evaluated after 35 days of treatment. MeHg caused an increase in TBARS and decreased NPSH levels in all tissues. MeHg also induced a decrease in hepatic ascorbic acid content and in renal GPx and CAT activities. Diphenyl diselenide (1 mg/kg) conferred protection against MeHg-induced hepatic and renal lipid peroxidation and at both doses prevented the reduction in hepatic NPSH levels. Diphenyl diselenide also conferred a partial protection against MeHg-induced oxidative stress (TBARS and NPSH) in liver and cerebellum. Of particular importance, diphenyl diselenide decreased the deposition of Hg in cerebrum, cerebellum, kidney and liver. The present results indicate that diphenyl diselenide can protect against some toxic effects of MeHg in mice. This protection may be related to its antioxidant properties and its ability to reduce Hg body burden. We posit that formation of a selenol intermediate, which possesses high nucleophilicity and high affinity for MeHg, accounts for the ability of diphenyl diselenide to ameliorate MeHg-induced toxicity.

Topics: Animals; Antioxidants; Ascorbic Acid; Benzene Derivatives; Brain; Catalase; Glutathione Peroxidase; Kidney; Lipid Peroxidation; Liver; Male; Mercury; Methylmercury Compounds; Mice; Neuroprotective Agents; Organoselenium Compounds; Oxidative Stress; Sulfhydryl Compounds; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances; Weight Gain

To validate the alkaline single cell gel (SCG) assay as a tool for the detection of DNA damage in human leukocytes, we investigated the in vitro activity of 18 chemicals. Thirteen of these chemicals (pyrene (PY), benzo(a)pyrene (BaP), cyclophosphamide (CP), 4-nitroquinoline-1-oxide (4NQO), bleomycin (BLM), methylmercury chloride (MMC), mitomycin C (MTC), hydrogen peroxide (HP), diepoxybutane (DEB), glutaraldehyde (GA), formaldehyde (FA), griseofulvin (GF), sodium azide (NA)) are genotoxic in at least one cell system, while five compounds (ascorbic acid (AA), glucose (GL), D-mannitol (MAN), O-vanillin (VAN), chlorophyllin (CHL)) are classified as non-genotoxic. In this in vitro SCG assay, PY, BaP and CP were positive with exogeneous metabolic activation (rat S9 mix) while 4NQO, BLM, MMC, MTC, hydrogen peroxide, and diepoxbutane were positive in the absence of metabolic activation. CHL and VAN were unexpectedly found to induce a dose-dependent increase in DNA migration. AA, GL, and MAN were negative in a non-toxic range of doses. GF gave equivocal results, while FA and GA increased DNA migration at low doses and decreased DNA migration at higher doses. This behaviour is consistent with the known DNA damaging and crosslinking properties of these compounds. These data support the sensitivity and specificity of this assay for identifying genotoxic agents.

Topics: 4-Nitroquinoline-1-oxide; Adult; Animals; Ascorbic Acid; Benzaldehydes; Benzo(a)pyrene; Biotransformation; Bleomycin; Chlorophyllides; Cyclophosphamide; DNA Damage; Epoxy Compounds; Female; Formaldehyde; Glucose; Glutaral; Griseofulvin; Humans; Hydrogen Peroxide; Hydrogen-Ion Concentration; Leukocytes; Mannitol; Methylmercury Compounds; Microsomes, Liver; Mitomycin; Mutagenicity Tests; Pyrenes; Rats; Reproducibility of Results; Sodium Azide

Antioxidants, namely cysteine, 2.46 x 10(-5) M; glutathione 9.75 x 10(-6), 9.75 x 10(-4) M; vitamin C, 10(-2) M; mannitol, 5 x 10(-2) M; potassium iodide, 5 x 10(-2) M and sodium selenite, 1.73 x 10(-6) M; were tested for their prophylactic activity against the genotoxicity of methylmercuric chloride, 1.26 x 10(-6) M and maleic hydrazide, 3 x 10(-4) M in Allium micronucleus assay. Antioxidants doses were administered simultaneously or prior to the genotoxic exposures. The results from the present experiments indicated that antioxidants conferred protection against the genotoxicity of both methyl mercuric chloride and maleic hydrazide. Furthermore, the protection of GSH against methyl mercuric chloride depending on the concentration persisted for 12 h.

Topics: Allium; Antimutagenic Agents; Antioxidants; Ascorbic Acid; Cysteine; DNA Damage; Glutathione; Maleic Hydrazide; Mannitol; Methylmercury Compounds; Micronucleus Tests; Potassium Iodide; Sodium Selenite

Effects of methylmercuric chloride (MMC) in the absence and presence of ascorbic acid on the synthesis of prostaglandins E2 and F2 alpha, and the lipid peroxidation of rabbit kidney medulla slices were studied. MMC showed dose-dependent inhibition of prostaglandins E2 and F2 alpha formation. The lipid peroxidation was not stimulated by MMC alone. Ascorbic acid plus MMC were able to stimulate the lipid peroxidation markedly, but the lipid peroxidation induced by ascorbic acid plus MMC had no influence on prostaglandin E2 production decreased by MMC alone. These results suggest that MMC inhibits prostaglandin formation by affecting the activity of prostaglandin cyclooxygenase, but that lipid peroxidation is not directly responsible for this inhibitory effect of MMC.

Topics: Animals; Ascorbic Acid; Dinoprost; Dinoprostone; In Vitro Techniques; Kidney Medulla; Lipid Peroxides; Male; Methylmercury Compounds; Prostaglandins; Prostaglandins E; Prostaglandins F; Rabbits

Topics: Animals; Ascorbic Acid; Cyprinidae; Goldfish; Inactivation, Metabolic; Mercuric Chloride; Mercury; Methylmercury Compounds