ABSTRACT
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.
Subject(s)
Benzene Derivatives/pharmacology , Brain/metabolism , Kidney/metabolism , Liver/metabolism , Mercury/metabolism , Methylmercury Compounds/toxicity , Organoselenium Compounds/pharmacology , Oxidative Stress/drug effects , Animals , Antioxidants/pharmacology , Ascorbic Acid/metabolism , Catalase/metabolism , Glutathione Peroxidase/metabolism , Lipid Peroxidation/drug effects , Male , Mice , Neuroprotective Agents/pharmacology , Sulfhydryl Compounds/metabolism , Superoxide Dismutase/metabolism , Thiobarbituric Acid Reactive Substances/metabolism , Weight Gain/drug effectsABSTRACT
Pharmacopoeias prescribe tests to determine the levels of arsenic in raw materials and glass containers. In this study, glass ampoules for injectables containing individually the main components of intravenous nutrition formulations were submitted to the hydrolytic resistance test by heating at 121 degrees C for 30 min. As(V) and As(III) levels in these solutions after heating were determined by hydride generation atomic absorption spectrometry. The arsenic content of substances used in these formulations was previously determined, as well as the arsenic content of the glass containers. The results showed that raw substances as well as glass containers contain arsenic. Moreover, arsenic is released during the heating (hydrolytic resistance test). However, the amount released and the arsenic species present in solution depend on the solution composition. While As(V) was the predominant specie in glass, solutions containing reducing substances such as glucose and vitamins had As(III) in higher concentration. Therefore, arsenic is released from glass containers during the heating for sterilization, and reacts with formulation constituents depending on their reducing properties.
