Effects of diphenyl diselenide on methylmercury toxicity in rats.
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.
Biochemistry and Molecular Biology Department, Graduation Program in Biological Sciences: Toxicological Biochemistry, Natural and Exact Sciences Center, Federal University of Santa Maria, 97105-900 Santa Maria, RS, Brazil.
Cristiane L
CL
Dalla Corte
Federal University of Pampa-Caçapava do Sul Campus, Avenida Pedro Anunciação, Vila Batista, 96570-000 Caçapava do Sul, RS, Brazil.
Caroline
C
Wagner
Federal University of Pampa-Caçapava do Sul Campus, Avenida Pedro Anunciação, Vila Batista, 96570-000 Caçapava do Sul, RS, Brazil.
Jéssie H
JH
Sudati
Higher Education Cenecista Institute of Santo Ângelo-IESA, Rua Dr. João Augusto Rodrigues 471, 98801-015 Santo Ângelo, RS, Brazil.
Bruna
B
Comparsi
Regional University of Cariri, Pharmacology and Molecular Chemistry Laboratory, Rua Cel. Antônio Luís 1161, 63100-000 Crato, CE, Brazil.
Gerlania O
GO
Leite
Biochemistry and Molecular Biology Department, Graduation Program in Biological Sciences: Toxicological Biochemistry, Natural and Exact Sciences Center, Federal University of Santa Maria, 97105-900 Santa Maria, RS, Brazil.
Alcindo
A
Busanello
Biochemistry and Molecular Biology Department, Graduation Program in Biological Sciences: Toxicological Biochemistry, Natural and Exact Sciences Center, Federal University of Santa Maria, 97105-900 Santa Maria, RS, Brazil.
Félix A A
FA
Soares
Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA ; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Michael
M
Aschner
Biochemistry and Molecular Biology Department, Graduation Program in Biological Sciences: Toxicological Biochemistry, Natural and Exact Sciences Center, Federal University of Santa Maria, 97105-900 Santa Maria, RS, Brazil.
João B T
JB
Rocha
D000818:Animals; D001555:Benzene Derivatives / Q000633:toxicity*; D001921:Brain / Q000187:drug effects; D004338:Drug Combinations; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008767:Methylmercury Compounds / Q000633:toxicity*; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D016566:Organoselenium Compounds / Q000633:toxicity*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013880:Thioredoxin-Disulfide Reductase / Q000096:biosynthesis / Q000187:drug effects
D001555:Benzene Derivatives; D004338:Drug Combinations; D008767:Methylmercury Compounds; D016566:Organoselenium Compounds; D017382:Reactive Oxygen Species; C061132:diphenyldiselenide; D013880:Thioredoxin-Disulfide Reductase