Diphenyl diselenide, a simple organoselenium compound, decreases methylmercury-induced cerebral, hepatic and renal oxidative stress and mercury deposition in adult mice.
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.
de Freitas
Andressa Sausen
AS
Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, CEP 97105-900 RS, Brazil.
Funck
Vinícius Rafael
VR
Rotta
Mariana dos Santos
Mdos S
Bohrer
Denise
D
Mörschbächer
Vanessa
V
Puntel
Robson Luís
RL
Nogueira
Cristina Wayne
CW
Farina
Marcelo
M
Aschner
Michael
M
Rocha
João Batista Teixeira
JB
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001205:Ascorbic Acid / Q000378:metabolism; D001555:Benzene Derivatives / Q000494:pharmacology*; D001921:Brain / Q000378:metabolism*; D002374:Catalase / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000378:metabolism*; D008297:Male; D008628:Mercury / Q000378:metabolism*; D008767:Methylmercury Compounds / Q000633:toxicity*; D051379:Mice; D018696:Neuroprotective Agents / Q000494:pharmacology; D016566:Organoselenium Compounds / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D015430:Weight Gain / Q000187:drug effects
D000975:Antioxidants; D001555:Benzene Derivatives; D008767:Methylmercury Compounds; D018696:Neuroprotective Agents; D016566:Organoselenium Compounds; D013438:Sulfhydryl Compounds; D017392:Thiobarbituric Acid Reactive Substances; C061132:diphenyldiselenide; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D008628:Mercury; D001205:Ascorbic Acid; C004925:methylmercuric chloride