title: 4-Methylpyrazole blocks acetaminophen hepatotoxicity in the rat.
abstract: 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.
  
  
  METHODS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Emergency Medicine, Albany Medical College, New York.
authors.forename: R J
authors.initials: RJ
authors.lastname: Brennan
authors.forename: R F
authors.initials: RF
authors.lastname: Mankes
authors.forename: R
authors.initials: R
authors.lastname: Lefevre
authors.forename: N
authors.initials: N
authors.lastname: Raccio-Robak
authors.forename: R H
authors.initials: RH
authors.lastname: Baevsky
authors.forename: J A
authors.initials: JA
authors.lastname: DelVecchio
authors.forename: B J
authors.initials: BJ
authors.lastname: Zink
mesh_terms: D000082:Acetaminophen / Q000009:adverse effects*; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D004305:Dose-Response Relationship, Drug; D000077604:Fomepizole; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008297:Male; D009336:Necrosis; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D011720:Pyrazoles; D000082:Acetaminophen; D000077604:Fomepizole; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase