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Relationship between debromination reaction of halogen compounds and organ toxicity

卤素化合物的脱溴反应与器官毒性的关系

基本信息

批准号：
60570131
负责人：
SUGIYAMA Toshihiro
金额：
$ 1.02万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1985
资助国家：
日本
起止时间：
1985 至 1986
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-60570131/
关键词：
debromination cytochrome P-450 cytochrome <b_5>halothane radical dibromoethane ジブロムエタン

项目摘要

Polyhalogenated alkanes are known to undergo anaerobic dehalogenation reaction to radical intermediates which induce liver injury. Recently it was revealed that cytochrome <b_5> (cyt.b5) reduces radical intermediates, indicating that cyt. <b_5> may participate in preventing cytotoxicities of polyhalogenated alkanes. To clarify the effect of cyt. <b_5> on the dehalogenation reaction, debrominations of halothane and 1,2-dibromoethane(DBE) were investigated in a reconstituted system containing phenobarbital-inducible P-450, NADPH-P-450 reductase, phospholipids, and NADPH under aerobic and anaerobic conditions. Liberated bromide ion was detected by bromide electrode. Under aerobic conditions, cyt. <b_5> enhanced the hydroxylations of halothane and DBE followed by <alpha> -elimination of bromide. A radical signal was detected by ESR only under anaerobic conditions. Under anaerobic conditions, halothane and DBE are known to undergo one electron reduction followed by <alpha> -elimination of bromide to form radical intermediates, and subsequently <beta> -elimination of halogens occurs when second electron is supplied. Cyt. <b_5> stimulated the anaerobic debromination rate of DBE, but did not affect the debromination of halothane possessing no bromine at <beta> -position. Thus, cyt. <b_5> seems to stimulate <beta> -elimination of halogens by supply of second electron, presumably resulting in the decrease of radical intermediates.

已知多卤代烷经厌氧脱卤反应生成自由基中间体，其诱导肝损伤。最近有人透露，细胞色素<b_5>（cyt.b5）减少自由基中间体，表明细胞色素。<b_5>可能参与防止多卤代烷烃的细胞毒性。阐明细胞色素的作用。<b_5>在含苯巴比妥诱导的P-450、NADPH-P-450还原酶、磷脂和NADPH的重组体系中，研究了在有氧和厌氧条件下氟烷和1，2-二溴乙烷（DBE）的脱溴反应。释放的溴离子由溴电极检测。在有氧条件下，细胞色素。<b_5>促进氟烷和DBE的羟基化，<alpha>随后消除溴化物。自由基信号检测ESR仅在厌氧条件下。在厌氧条件下，已知氟烷和DBE经历一个电子还原，<alpha>然后溴离子消除以形成自由基中间体，并且随后<beta>当提供第二个电子时发生卤素消除。Cyt. <b_5>对DBE的厌氧脱溴速率有一定的促进作用，但对-位无溴的氟烷的脱溴反应没有影响<beta>。因此，Cyt。<b_5>似乎刺激<beta>-消除卤素供应的第二个电子，大概导致自由基中间体的减少。