4-METHYLPYRAZOLE BLOCKS ACETAMINOPHEN HEPATOTOXICITY IN THE RAT
4-METHYLPYRAZOLE BLOCKS ACETAMINOPHEN HEPATOTOXICITY IN THE RAT
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DOI：
10.1016/s0196-0644(94)70067-2
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发表时间：
1994-03-01
影响因子：
6.2
通讯作者：
ZINK, BJ
中科院分区：
文献类型：
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作者：
BRENNAN, RJ;MANKES, RF;ZINK, BJ
研究目的：为了确定4-甲基吡唑是否抑制对乙酰氨基酚在大鼠模型中的肝毒性作用，参与者的设计和类型：使用雄性Sprague-Dawley大鼠的非盲实验。第1组至第3组通过灌胃给予2，000 mg/kg对乙酰氨基酚;第4组作为对照。在4或8小时，第2组接受400 mg/kg 4-甲基吡唑;第3组接受50 mg/kg 4-甲基吡唑。采集血液样品用于测量血清AST和ALT水平。结果：对乙酰氨基酚给药后4小时，400 mg/kg（P <0.01）和50 mg/kg（P <0.05）剂量的4-甲基吡唑均降低了AST和ALT水平。尽管在对乙酰氨基酚给药后8小时给予400和50 mg/kg 4-甲基吡唑时，平均AST和ALT水平也较低，但这些结果无统计学显著性。仅接受对乙酰氨基酚的大鼠的中位坏死评分为3分，接受对乙酰氨基酚和400 mg/kg 4-甲基吡唑的大鼠为0.5分（P <0.05），1例接受对乙酰氨基酚和50 mg/kg 4-甲基吡唑（P < .05），对照组0（P < .05）。结论：当在毒性剂量的对乙酰氨基酚后4小时给药时，4-甲基吡唑显著抑制大鼠的肝毒性，这反映在血清转氨酶水平较低和肝坏死程度较轻。
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.