Abstract
Hydrogen sulfide (H
2S), 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 H
2S against acetaminophen-induced hepatotoxicity.
Male Swiss mice were treated with sodium hydrogen sulfide, a H
2S donor, 30
min after acetaminophen administration. N-acetylcysteine, a therapeutic antidote, was used as a reference drug.
H
2S 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. H
2S did not alter catalase activity. Additionally, immunohistochemical analysis demonstrated that H
2S 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 H
2S were confirmed by liver histopathological examination and were maintained in the presence of glibenclamide, an antagonist of ATP-sensitive potassium (K
ATP) channels.
H
2S 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 K
ATP channels. The hepatocurative effects of H
2S are comparable to N-acetylcysteine. Hence, H
2S has a potential therapeutic value for treatment of acetaminophen hepatotoxicity.