Title: Effects of diphenyl diselenide on methylmercury toxicity in rats.
Authors: Dalla Corte, Cristiane L; Wagner, Caroline; Sudati, Jéssie H; Comparsi, Bruna; Leite, Gerlania O; Busanello, Alcindo; Soares, Félix A A; Aschner, Michael; Rocha, João B T
Published In Biomed Res Int, (2013)
Abstract: This study investigates the efficacy of diphenyl diselenide [(PhSe)2] in attenuating methylmercury- (MeHg-)induced toxicity in rats. Adult rats were treated with MeHg [5 mg/kg/day, intragastrically (i.g.)] and/ or (PhSe)2 [1 mg/kg/day, intraperitoneally (i.p.)] for 21 days. Body weight gain and motor deficits were evaluated prior to treatment, on treatment days 11 and 21. In addition, hepatic and cerebral mitochondrial function (reactive oxygen species (ROS) formation, total and nonprotein thiol levels, membrane potential (ΔΨm), metabolic function, and swelling), hepatic, cerebral, and muscular mercury levels, and hepatic, cerebral, and renal thioredoxin reductase (TrxR) activity were evaluated. MeHg caused hepatic and cerebral mitochondrial dysfunction and inhibited TrxR activity in liver (38,9%), brain (64,3%), and kidney (73,8%). Cotreatment with (PhSe)2 protected hepatic and cerebral mitochondrial thiols from depletion by MeHg but failed to completely reverse MeHg's effect on hepatic and cerebral mitochondrial dysfunction or hepatic, cerebral, and renal inhibition of TrxR activity. Additionally, the cotreatment with (PhSe)2 increased Hg accumulation in the liver (50,5%) and brain (49,4%) and increased the MeHg-induced motor deficits and body-weight loss. In conclusion, these results indicate that (PhSe)2 can increase Hg body burden as well as the neurotoxic effects induced by MeHg exposure in rats.
PubMed ID: 24459674
MeSH Terms: Animals; Benzene Derivatives/toxicity*; Brain/drug effects; Drug Combinations; Kidney/drug effects; Liver/drug effects; Methylmercury Compounds/toxicity*; Mitochondria/drug effects*; Mitochondria/enzymology; Mitochondria/pathology; Organoselenium Compounds/toxicity*; Rats; Reactive Oxygen Species/metabolism; Thioredoxin-Disulfide Reductase/biosynthesis; Thioredoxin-Disulfide Reductase/drug effects