Curative effects of hydrogen sulfide against acetaminophen-induced hepatotoxicity in mice

Abstract

Aims: Hydrogen sulfide (H2S), an endogenous gaseous mediator, plays an important role in regulation of many physiological and pathological processes. On the other hand, acetaminophen overdose is a major cause of drug-induced liver failure. The aim of this study therefore is to evaluate the possible curative effects of H2S against acetaminophen-induced hepatotoxicity. Main methods: Male Swiss mice were treated with sodium hydrogen sulfide, a H2S donor, 30min after acetaminophen administration. N-acetylcysteine, a therapeutic antidote, was used as a reference drug. Key findings: H2S treatment resulted in hepatocurative effects as evident by a significant decrease in serum alanine aminotransferase and hepatic malondialdehyde and nitric oxide levels, with a concurrent increase in hepatic glutathione content compared to acetaminophen-treated group. H2S did not alter catalase activity. Additionally, immunohistochemical analysis demonstrated that H2S treatment markedly reduced tumor necrosis factor-α expression, while expression of cyclooxygenase-2 was markedly enhanced with nuclear localization into hepatocytes. The curative effects of H2S were confirmed by liver histopathological examination and were maintained in the presence of glibenclamide, an antagonist of ATP-sensitive potassium (KATP) channels. Significance: H2S treatment markedly alleviates acetaminophen hepatotoxicity in mice possibly, in part, through anti-oxidative and anti-inflammatory effects but not likely to be coupled with activation of KATP channels. The hepatocurative effects of H2S are comparable to N-acetylcysteine. Hence, H2S has a potential therapeutic value for treatment of acetaminophen hepatotoxicity. © 2010 Elsevier Inc.