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Protective effect of p ‐methoxyl‐diphenyl diselenide in lethal acute liver failure induced by lipopolysaccharide and d ‐galactosamine in mice
Author(s) -
Wilhelm E.A.,
Jesse C.R.,
Nogueira C.W.
Publication year - 2009
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/j.1472-8206.2009.00759.x
Subject(s) - diphenyl diselenide , lipopolysaccharide , galactosamine , liver failure , diselenide , pharmacology , chemistry , medicine , toxicology , biochemistry , biology , selenium , organic chemistry , glucosamine
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 μg/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.