Curative effects of hydrogen sulfide against acetaminophen-induced hepatotoxicity in mice.
OBJECTIVE
Hydrogen sulfide (H(2)S), 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(2)S against acetaminophen-induced hepatotoxicity.


METHODS
Male Swiss mice were treated with sodium hydrogen sulfide, a H(2)S donor, 30 min after acetaminophen administration. N-acetylcysteine, a therapeutic antidote, was used as a reference drug.


RESULTS
H(2)S 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(2)S did not alter catalase activity. Additionally, immunohistochemical analysis demonstrated that H(2)S 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(2)S were confirmed by liver histopathological examination and were maintained in the presence of glibenclamide, an antagonist of ATP-sensitive potassium (K(ATP)) channels.


CONCLUSIONS
H(2)S 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(2)S are comparable to N-acetylcysteine. Hence, H(2)S has a potential therapeutic value for treatment of acetaminophen hepatotoxicity.
Morsy
Mohamed A
MA
Department of Pharmacology, Faculty of Medicine, El-Minia University, El-Minia, Egypt. mamm222@hotmail.com
Ibrahim
Salwa A
SA
Abdelwahab
Soha A
SA
Zedan
Mervat Z
MZ
Elbitar
Hussien I
HI
D000082:Acetaminophen / Q000633:toxicity*; D000111:Acetylcysteine / Q000494:pharmacology; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000931:Antidotes / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D051546:Cyclooxygenase 2 / Q000187:drug effects / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D000931:Antidotes; D000975:Antioxidants; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D000082:Acetaminophen; D008315:Malondialdehyde; D051546:Cyclooxygenase 2; D000410:Alanine Transaminase; D005978:Glutathione; D000111:Acetylcysteine; D006862:Hydrogen Sulfide