Post-treatment protection with piperonyl butoxide against acetaminophen hepatotoxicity is associated with changes in selective but not total covalent binding.
Post-treatment protection with piperonyl butoxide against acetaminophen hepatotoxicity is associated with changes in selective but not total covalent binding.
复制标题
胡椒基丁醚针对对乙酰氨基酚肝毒性的治疗后保护与选择性而非总共价结合的变化相关。
DOI：
10.1007/978-1-4684-5877-0_88
复制
发表时间：
1991
影响因子：
--
通讯作者：
Cohen,SD
中科院分区：
文献类型：
--
作者：
Brady,JT;Birge,RB;Khairallah,EA;Cohen,SD
对乙酰氨基酚(APAP)诱导的肝小叶中心坏死与细胞色素P-450介导的亲电活性代谢物的生成有关，当谷胱甘肽耗尽时，该代谢物与细胞大分子共价结合(Jollow等人，1973；Mitchell等人，1973a；1973b；Potter等人，1973；1974)。共价结合与肝坏死的发生率和严重程度密切相关，先前的细胞色素P450抑制既能阻断共价结合又能阻断细胞毒性(Jollow等人，1973；Potter等人，1973,1974；Mitchell等人，1973a)。此外，在APAP后2小时给予细胞色素P-450抑制剂胡椒基丁醚(Pip B)，达到最大共价结合的时间(Jollow等人，1973，Ginsberg和Cohen，1985)降低了肝脏损伤的严重程度(Brady，等人，1988)。本研究表明，Pip B的处理后保护与APAP选择性蛋白质芳基化的改变有关，而不改变总的共价结合。
Acetaminophen (APAP) induced hepatic centrilobular necrosis has been associated with cytochrome P-450-mediated generation of an electrophilic, reactive metabolite which covalently binds to cellular macromolecules as glutathione becomes depleted (Jollow, et al., 1973; Mitchell, et al., 1973a; 1973b; Potter, et al., 1973; 1974). Covalent binding has been well-correlated with the incidence and severity of liver necrosis and prior cytochrome P450 inhibition blocks both covalent binding and the atotoxicity (Jollow, et al., 1973; Potter, et al., 1973, 1974; Mitchell, et al., 1973a). In addition, administration of the cytochrome P-450 inhibitor, piperonyl butoxide (Pip B), 2 hrs after APAP, the time of maximal covalent binding (Jollow,et al., 1973, Ginsberg and Cohen, 1985) reduced the severity of liver damage (Brady, et al., 1988). The present study demonstrates that Pip B’s post-treatment protection is associated with alterations in selective protein arylation by APAP without a change in total covalent binding.