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4-Methylpyrazole blocks acetaminophen hepatotoxicity in the rat
R J Brennan1, R F Mankes, R Lefevre
1Department of Emergency Medicine, Albany Medical College, New York.
Study Objective:
To determine whether 4-methylpyrazole inhibits the hepatotoxic effects of acetaminophen in a rat model. DESIGN AND TYPE OF PARTICIPANTS: A nonblinded experiment using male Sprague-Dawley rats.
Interventions:
Animals were divided into four groups. Groups 1 through 3 received 2,000 mg/kg acetaminophen by gavage; group 4 acted as a control. At four or eight hours, group 2 received 400 mg/kg 4-methylpyrazole; group 3 received 50 mg/kg 4-methylpyrazole. Blood samples were taken for measurements of serum AST and ALT levels. Livers were removed for microscopic examination and grading of necrosis.
Results:
Lower AST and ALT levels were obtained for both the 400-mg/kg (P < .01) and 50-mg/kg (P < .05) doses of 4-methylpyrazole administered four hours after acetaminophen. Although mean AST and ALT levels also were lower when 400 and 50 mg/kg 4-methylpyrazole were administered eight hours after acetaminophen, these results were not statistically significant. Median necrosis scores were 3 for rats receiving acetaminophen alone, 0.5 for those receiving acetaminophen and 400 mg/kg 4-methylpyrazole (P < .05), 1 for those receiving acetaminophen and 50 mg/kg 4-methylpyrazole (P < .05), and 0 for control rats (P < .05).
Conclusion:
When administered four hours after a toxic dose of acetaminophen, 4-methylpyrazole significantly inhibits hepatotoxicity in the rat, as reflected by lower levels of serum transaminases and lesser degrees of hepatic necrosis.