The protecting effect of L-carnitine in septic damage in rat mitochondria

本研究旨在探讨黄嘌呤-黄嘌呤氧化酶和脂多糖系统对大鼠肝线粒体氧化应激的影响及肉毒碱的保护作用。暴露于自由基中的线粒体在NAD ^1连接的底物的支持下表现出显著的O^2消耗，但在琥珀酸盐和抗坏血酸盐的存在下，O^2消耗几乎没有变化。氧化应激中肉毒碱的存在导致线粒体呼吸恢复到对照值的程度。氧化应激导致线粒体内烟酰胺核苷酸的丢失，而添加NAD ^1完全阻止了NAD ^1连接的底物消耗O^2的任何失败。电子转移复合物1的活性和琥珀酸对NAD ^1的能量依赖性还原不受氧化应激的影响。线粒体肿胀的程度密切相关的状态-3氧化的抑制和状态-4氧化琥珀酸的增加。肉毒碱可防止氧自由基引起的线粒体损伤（肿胀、Ca^2释放、蔗糖捕获解偶联）。这些发现表明，在本实验系统中，自由基对线粒体的有害作用是由Ca^2依赖性膜转换触发的，而肉毒碱在分离的线粒体中的保护作用是阻止线粒体通透性转换的能力的结果。

The purpose of this study was to evaluate the possible involvement of oxidative stress derived from xanthine-xanthine oxidase and LPS system in rat liver mitochondria and the possible protective effect of carnitine. Mitochondria exposed to free radicals exhibited a significant degree in O^2 consumption supported by NAD^1 linked substrates, but showed almost no change in O^2 consumption in the presence of succinate and ascorbate. The presence of carnitine in oxidative stress caused the recovery of mitochondrial respiration to retern the degree of control values. Oxidative stress caused the loss of intramitochondrial nicotinamide nucleotides, and addition of NAD^1 fully prevented any fail in O^2 consumption with NAD^1 linked substrates. the activity of electron-transfer complex 1 and the energy dependent reduction of NAD^1 by succinate were unaltered by oxidative stress. The degree of mitochondrial swelling was closely correlated with the inhibition of State-3 oxidation and with the increase in the State-4 oxidation of succinate. The carnitine prevented the mitochondrial damage (swelling, Ca^2 release, sucrose trapping uncoupling) induced by oxygen free radicals. These findings suggest that the deleterious effect of free radicals on mitochondria in the present experimental system was triggered by Ca^2 dependent membrane transition and carnitine to protect in isolated mitochondria is a consequence of the ability to prevent the mitochondrial permeability transition.