4-METHYLPYRAZOLE BLOCKS ACETAMINOPHEN HEPATOTOXICITY IN THE RAT

被引：10

作者：

BRENNAN, RJ ^{[1
]}

MANKES, RF ^{[1
]}

LEFEVRE, R ^{[1
]}

RACCIOROBAK, N ^{[1
]}

BAEVSKY, RH ^{[1
]}

DELVECCHIO, JA ^{[1
]}

ZINK, BJ ^{[1
]}

机构：

[1] ALBANY MED COLL,DEPT EMERGENCY MED,ALBANY,NY 12208

来源：

ANNALS OF EMERGENCY MEDICINE | 1994年 / 23卷 / 03期

关键词：

D O I：

10.1016/S0196-0644(94)70067-2

中图分类号：

R4 [临床医学];

学科分类号：

1002 ; 100602 ;

摘要：

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.

引用

页码：487 / 493

页数：7

共 54 条

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