Protective effects of 4-methylpyrazol in comparison with n acetylcysteine against acetaminophen-induced hepatotoxicity in rats

ABSTRACT

N- Acetylcysteine [NAC] is the only available antidote for acetaminophen [APAP] poisoning. 4- Methylpyrazole [4-MP]. a well-known inhibitor of alcohol dehydrogenase, has also been shown to inhibit CYP2El [one of the cytochrome P450 system] which has been identified to be involved in APAP bio activation in human beings. The aim of this study was to evaluate the hepatoprotective effect of 4-MP in comparison with NAC against APAP- induced hepatic necrosis in rats. APAP [2.000, g/kg] was given to 6 groups of animals by gavage; group 7 acted as control. After 4 hours. group 3 received 4-MP [200 mg/kg] orally; group 4 received 200 my/kg 4- MP followed by 4 doses at 12 hours intervals; group 5 received 140 mg/kg NAC and group 6 received 140 mg/ kg NAC followed by 70 mg/kg every 4 hours for 12 doses. The results obtained from this study indicated that the administration of 4-MP or NAC [both single and repeated - dose regimen] after 4 hours toxic dose of APAP significantly inhibited hepatotoxicity in the rate with little superiority of 4-MP as reflected by significantly lower levels of serum transaminases [AST and ALT] and lesser degrees of hepatic necrosis