title: Protective effect of p-methoxyl-diphenyl diselenide in lethal acute liver failure induced by lipopolysaccharide and D-galactosamine in mice.
abstract: Organoselenium compounds display important antioxidant activity and many biological activities interesting from pharmacological point of view. The aim of this study was to evaluate the hepatoprotective effect of p-methoxyl-diphenyl diselenide, a disubstituted diaryl diselenide, on acute liver injury induced by D-galactosamine (D-GalN) and lipopolysaccharide (LPS) in mice. The animals received p-methoxyl-diphenyl diselenide (10, 50 and 100 mg/kg; per oral, p.o.) and 1 h after d-GalN (500 mg/kg) and LPS (50 microg/kg) were administered by intraperitoneal route (i.p.). Twenty-four hours after LPS/d-GalN exposure the animals were euthanized to the biochemical and histological analysis. Pretreatment with p-methoxyl-diphenyl diselenide (50 and 100 mg/kg; p.o.) protected against the increase in aspartate aminotransferase (AST) activity induced by LPS/d-GalN exposure in mice. p-Methoxyl-diphenyl diselenide at the doses of 50 and 100 mg/kg protected against the increase in alanine aminotransferase (ALT) activity induced by LPS/D-GalN exposure. In this study, no alteration in ascorbic acid levels was observed in livers of mice exposed to LPS/D-GalN. Glutathione-S-transferase (GST) activity was stimulated by LPS/D-GalN exposure and p-methoxyl-diphenyl diselenide, at all doses, protected against this alteration. p-Methoxyl-diphenyl diselenide was effective in ameliorating inhibition of catalase activity induced by LPS/d-GalN exposure. Histological data showed that sections of livers from LPS/D-GalN-treated mice presented massive hemorrhage, inflammatory cells and necrosis. p-Methoxyl-diphenyl diselenide significantly attenuated LPS/D-GalN-induced hepatic histopathological alterations. Based on the results, we suggest the hepatoprotective effect of p-methoxyl-diphenyl diselenide on acute liver injury induced by LPS/d-GalN exposure in mice.
authors.affiliation: Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios, Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.
authors.forename: E A
authors.initials: EA
authors.lastname: Wilhelm
authors.forename: C R
authors.initials: CR
authors.lastname: Jesse
authors.forename: C W
authors.initials: CW
authors.lastname: Nogueira
mesh_terms: D000284:Administration, Oral; D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D001205:Ascorbic Acid / Q000378:metabolism; D001219:Aspartate Aminotransferases / Q000378:metabolism; D001555:Benzene Derivatives / Q000494:pharmacology / Q000627:therapeutic use*; D002374:Catalase / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D005688:Galactosamine; D005982:Glutathione Transferase / Q000378:metabolism; D007274:Injections, Intraperitoneal; D008070:Lipopolysaccharides; D017114:Liver Failure, Acute / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D016566:Organoselenium Compounds / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000975:Antioxidants; D001555:Benzene Derivatives; D008070:Lipopolysaccharides; D016566:Organoselenium Compounds; C528548:p-methoxy-diphenyl diselenide; D005688:Galactosamine; D002374:Catalase; D005982:Glutathione Transferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D001205:Ascorbic Acid