Relationship between debromination reaction of halogen compounds and organ toxicity

众所周知，多卤代烷烃会与自由基中间体发生厌氧脱卤化反应，从而导致肝脏损伤。最近发现细胞色素&lt；b_5&gt；(cyt.b5)能减少自由基中间体，表明细胞色素b_5和细胞色素b_5具有协同作用。可能参与预防多卤代烷烃的细胞毒性。阐明细胞色素T的作用。研究了在好氧和厌氧条件下，由苯巴比妥诱导的P-450、NADPH-P-450还原酶、磷脂和NADPH组成的重组体系中氟烷和1，2-二溴乙烷(DBE)的脱溴反应。用溴化物电极法测定释放的溴离子。在好氧条件下，Cyt.&lt；b_5&gt；增强了氟烷和DBE的羟基化反应，随后&lt；α&>-消除了溴。只有在厌氧条件下，ESR才能检测到自由基信号。在厌氧条件下，氟烷和DBE会经历一个电子还原，然后-lt；α-消除溴化物形成自由基中间体，随后-lt；β&>-卤素的消除发生在提供第二个电子的情况下。网络电话公司。促进了DBE的厌氧脱溴速率，但不影响β-位不含溴的氟烷脱溴。因此，Cyt.~lt；b_5&gt；似乎通过提供第二电子来刺激~lt；β&gt；消除卤素，推测这可能导致自由基中间体的减少。

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.