Immunochemical detection of drug-protein adducts in acetaminophen hepatotoxicity.

Immunochemical detection of drug-protein adducts in acetaminophen hepatotoxicity.
复制标题

对乙酰氨基酚肝毒性中药物-蛋白质加合物的免疫化学检测。

DOI:
10.1007/978-1-4757-9480-9_7
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发表时间:
1996
影响因子:
--
通讯作者:
Pumford,NR
Pumford,NR
中科院分区:
医学4区
文献类型:
--
作者:
Hinson,JA;Roberts,DW;Halmes,NC;Gibson,JD;Pumford,NR

文献摘要

被引文献

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In overdose the over-the-counter analgesic acetaminophen may produce a centrilobular hepatic necrosis (1,2). In addition this toxicity may be accompanied by nephrotoxicity (1,3). The mechanism of hepatotoxicity has been studied extensively in experimental animals. It was shown that inhibition of the drug metabolizing enzymes resulted in a diminution of the toxicity, whereas induction of the drug metabolizing enzymes resulted in an increase in the toxicity (4). These data indicated that metabolism of acetaminophen was critical in the development of the toxicity. Moreover, administration of radiolabeled acetaminophen resulted in covalent binding of radiolabel to protein in the necrotic hepatocytes (5).In vitroexperiments revealed that the metabolism was by a cytochrome P-450 dependent mechanism (6). It was postulated that covalent binding of this metabolite to critical proteins was the mechanism of the hepatotoxicity.