title: Oral administration of diphenyl diselenide potentiates hepatotoxicity induced by carbon tetrachloride in rats.
abstract: Carbon tetrachloride (CCl4) is a model for studying free radical-induced liver injury and screening hepato-protective drugs. Numerous studies have reported the involvement of oxidative stress in CCl4-induced liver damage and the hepato-protective effects mediated by different antioxidants. The present study examined the effects of diphenyl diselenide, (PhSe)2, on hepatotoxicity induced by CCl4 in rats. To this end, male Wistar rats received (PhSe)2 by oral route at the dosage of 31.2 mg/kg for one or two days. After the second day of treatment, rats received CCl4 orally in a single dose. The liver and kidney were utilized for determination of histopathology, biochemical [aspartate (ALT) and alanine (AST) aminotransferases, alkaline phosphatase (ALP), total bilirrubin (TB) and gamaglutamyl transferase (GGT)] and toxicological parameters [thiobarbituric reactive species (TBARS) levels, catalase activity, ascorbic acid, nonprotein thiols (NPSH) and aminolevulinate dehydratase (-ALA-D) activity]. Repeated administration of (PhSe)2 caused a marked potentiation of hepatotoxicity induced by CCl4 exposure, as manifested by an increase in biochemical parameters (AST, ALT, ALP, GGT and BT) and severe alteration in histopathology. This study also demonstrated a potentiation of TBARS levels and a consequent depletion of important antioxidant defenses including catalase and ascorbic acid. Pre-treatment with a single dose of (PhSe)2 prevented the effect of strychnine, a substrate for CYPs, abolishing lethality in mice. This result indicates that (PhSe)2 prevented animal death, suggesting an activator action of (PhSe)2 in CYPs. This study clearly indicates that (PhSe)2 potentiated acute hepatic damage induced by CCl4.
authors.affiliation: Departamento de Quimica, Centro de Ciencias Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, CEP 97105-900, RS, Brazil. criswn@quimica.ufsm.br
authors.forename: Cristina W
authors.initials: CW
authors.lastname: Nogueira
authors.forename: Lysandro Pinto
authors.initials: LP
authors.lastname: Borges
authors.forename: Ana Cristina Guerra
authors.initials: AC
authors.lastname: Souza
mesh_terms: D000284:Administration, Oral; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001205:Ascorbic Acid / Q000032:analysis / Q000378:metabolism; D001219:Aspartate Aminotransferases / Q000097:blood; D001555:Benzene Derivatives / Q000008:administration & dosage* / Q000494:pharmacology*; D001663:Bilirubin / Q000097:blood; D002251:Carbon Tetrachloride / Q000633:toxicity*; D002252:Carbon Tetrachloride Poisoning / Q000378:metabolism / Q000473:pathology; D002374:Catalase / Q000032:analysis / Q000378:metabolism; D003404:Creatinine / Q000032:analysis; D004357:Drug Synergism; D064420:Drug-Related Side Effects and Adverse Reactions / Q000378:metabolism / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D016566:Organoselenium Compounds / Q000008:administration & dosage* / Q000494:pharmacology*; D000623:Porphobilinogen Synthase / Q000032:analysis / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis / Q000378:metabolism; D014508:Urea / Q000097:blood; D005723:gamma-Glutamyltransferase / Q000097:blood
chemical_list: D001555:Benzene Derivatives; D016566:Organoselenium Compounds; D017392:Thiobarbituric Acid Reactive Substances; C061132:diphenyldiselenide; D014508:Urea; D003404:Creatinine; D002251:Carbon Tetrachloride; D002374:Catalase; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000623:Porphobilinogen Synthase; D001205:Ascorbic Acid; D001663:Bilirubin