Laboratory of Cell Pathology, Institute of Cytology RAS, Tikhoretski Ave., 4, St. Petersburg, 194064, Russia.
J Bioenerg Biomembr. 2009 Aug;41(4):379-85. doi: 10.1007/s10863-009-9234-6. Epub 2009 Oct 10.
The progression of toxic hepatitis is accompanied by the activation of oxidative processes in the liver associated with an enhancement of the mitochondrial respiratory chain activity and superoxide anion production (O(2)(-)). The purpose of this study was to examine our previously formulated assumption concerning the predominant contribution of the complex I to O(2)(-) production increase by the mitochondrial respiratory chain of hepatocytes in toxic hepatitis (Shiryaeva et al. Tsitologiia, 49, 125-132 2007). Toxic hepatitis was induced by a combined application of CCl(4) and ethanol. Respiratory chain function analysis was executed with submitochondrial particles (SP) in the presence of specific inhibitors. It was shown that the rate of O(2)(-) production by SP of animals with toxic hepatitis, when NADH was delivered, was 2.5-fold higher as compared with the control. The rates of O(2)(-) production by SP of rats with toxic hepatitis in the presence of NADH or NADH+ rotenone were similar. The O(2)(-) production rate by control SP in the presence of NADH + rotenone corresponded to the O(2)(-) production rate by toxic hepatitis SP when only NADH was delivered. When NADH+ myxothiazol were delivered to the incubation system, O(2)(-) production by toxic hepatitis SP was 72% higher than for the control. Conversely, in the presence of antimycin A, the production of O(2)(-) by toxic hepatitis SP was lower compared to the control. Collectively, the presented data indicate that the O(2)(-) production rate was enhanced by the complex I of the hepatocyte mitochondrial respiratory chain in experimental toxic hepatitis. Complex III contribution to the production of O(2)(-) was insignificant. We assume that the increase in O(2)(*-) production by the respiratory chain may be considered not only as the mechanism of pathology progression, but also as a compensatory mechanism preserving the electron transport function of the mitochondrial respiratory chain when complex I functioning is blocked in part.
中毒性肝炎的进展伴随着肝脏氧化过程的激活，与线粒体呼吸链活性和超氧阴离子产生（O(2)(-)）的增强有关。本研究的目的是检验我们之前提出的假设，即中毒性肝炎时肝细胞线粒体呼吸链中复合物 I 对 O(2)(-)产生增加的主要贡献（Shiryaeva 等人，Tsitologiia，49，125-132，2007）。中毒性肝炎是通过 CCl(4)和乙醇联合应用诱导的。呼吸链功能分析是在存在特异性抑制剂的情况下用亚线粒体颗粒（SP）进行的。结果表明，当提供 NADH 时，中毒性肝炎动物的 SP 产生 O(2)(-)的速率比对照高 2.5 倍。当存在 NADH 或 NADH+鱼藤酮时，中毒性肝炎大鼠的 SP 产生 O(2)(-)的速率相似。当仅提供 NADH 时，对照 SP 在存在 NADH+鱼藤酮的情况下产生的 O(2)(-)的速率与仅提供 NADH 时中毒性肝炎 SP 产生的 O(2)(-)的速率相对应。当向孵育系统中提供 NADH+米噻唑时，中毒性肝炎 SP 产生的 O(2)(-)比对照高 72%。相反，当存在抗霉素 A 时，中毒性肝炎 SP 产生的 O(2)(-)比对照低。综上所述，所提供的数据表明，在实验性中毒性肝炎中，肝细胞线粒体呼吸链的复合物 I 增强了 O(2)(-)的产生速率。复合物 III 对 O(2)(-)产生的贡献可以忽略不计。我们假设，呼吸链产生的 O(2)(*-)增加不仅可以作为病理进展的机制，而且可以作为当部分阻断复合物 I 功能时，电子传递功能在线粒体呼吸链中被部分阻断的情况下的一种补偿机制。
