In vitro effects of 10, 10'-oxybisphenoxarsine on isolated rat liver mitochondria.
In vitro effects of 10, 10'-oxybisphenoxarsine on isolated rat liver mitochondria.
复制标题
10, 10-氧双酚胂对离体大鼠肝线粒体的体外影响。
DOI：
10.1016/0041-008x(82)90126-0
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发表时间：
1982
影响因子：
3.8
通讯作者：
Brabec,MJ
中科院分区：
文献类型：
--
作者：
Kronenberg,JM;Brabec,MJ
10，10 ′-氧代双苯恶胂（OBPA）是一种三价杂环有机砷化合物，是一种广谱有效的抗菌剂，常用于增塑聚氯乙烯中。虽然具有很高的毒性，但OBPA毒性的机制尚不清楚。由于其具有肝毒性，我们研究了OBPA对大鼠肝线粒体的体外影响。将分离的线粒体与1至8 μm OBPA孵育，并通过极谱法监测氧消耗。α-酮戊二酸、丙酮酸、异柠檬酸和琥珀酸的状态3呼吸被迅速抑制。OBPA也解偶联氧化磷酸化，虽然这是掩盖，在较高浓度下，进行性呼吸抑制。电子传递链出现不受OBPA，测量NADH氧化，但几个三羧酸循环酶被抑制。这种抑制被阻止，在某些情况下，逆转谷胱甘肽。很可能，OBPA，像其他三价有机砷，发挥其毒性作用，与重要的线粒体巯基反应。
10,10′-Oxybisphenoxarsine (OBPA), a trivalent, heterocyclic organoarsenical, is a potent, broad spectrum antimicrobial agent often incorporated into plasticized polyvinyl chlorides. Although highly toxic, the mechanism of OBPA toxicity is unknown. Since it is hepatotoxic, we investigated the in vitro effects of OBPA on rat liver mitochondria. Isolated mitochondria were incubated with 1 to 8 μm OBPA and oxygen consumption was monitored polarographically. State 3 respiration of α-ketoglutarate, pyruvate, isocitrate, and succinate was rapidly inhibited. OBPA also uncoupled oxidative phosphorylation, although this was masked, at higher concentrations, by progressive respiratory inhibition. The electron transport chain appeared unaffected by OBPA, as measured by NADH oxidation, but several tricarboxcylic acid cycle dehydrogenases were inhibited. This inhibition was prevented and, in some cases, reversed by glutathione. It is likely that OBPA, like other trivalent organoarsenicals, exerts its toxic effects by reacting with vital mitochondrial sulfhydryl groups.