Thürich T, Bereiter-Hahn J, Schneider M, Zimmer G
Gustav-Embden-Zentrum der Biologischen Chemie, Arbeitsgruppe Membranstruktur.
Arzneimittelforschung. 1998 Jan;48(1):13-21.
Rat hearts hypertrophied by exposure of the animals to low oxygen pressure were perfused by the Langendorff technique. After oxidative stress induced by hypoxia/reoxygenation, functional recovery of the hypertrophied right heart was insufficient when compared to non-hypertrophied controls. Accordingly, mitochondrial membrane potential did not recover sufficiently. There was a positive trend for improvement of the rate-pressure product during reoxygenation in lipoic acid (CAS 1077-28-7; 0.8 mumol/l) treated hearts which was also verified for membrane potential. Adenosine 5'-triphosphate and creatine phosphate contents as well as the ATP/ADP ratio in hypertrophied right ventricle were significantly increased after reoxygenation in hearts treated with lipoic acid. With lipoic acid, there was a significantly higher content of glutathione (oxidized form) after reoxygenation, Ca2+ uptake was significantly increased in mitochondria isolated from hypertrophied right ventricles and treated by 12 nmol/mg protein of lipoic acid. The results reveal a distinct improvement of mitochondrial structure/function by lipoic acid and suggest for therapy a combination with the synergistic free radical scavenging properties of tocopherol (CAS 10191-41-0).
通过将动物暴露于低氧压力使其心脏肥大的大鼠,采用Langendorff技术进行灌注。在缺氧/复氧诱导氧化应激后,与未肥大的对照组相比,肥大的右心功能恢复不足。因此,线粒体膜电位也没有充分恢复。在经硫辛酸(CAS 1077-28-7;0.8 μmol/l)处理的心脏复氧过程中,心率-血压乘积有改善的积极趋势,这在膜电位方面也得到了验证。经硫辛酸处理的心脏复氧后,肥大右心室中的三磷酸腺苷和磷酸肌酸含量以及ATP/ADP比值显著增加。使用硫辛酸后,复氧后谷胱甘肽(氧化形式)含量显著更高,从肥大右心室分离并经12 nmol/mg蛋白硫辛酸处理的线粒体中Ca2+摄取显著增加。结果显示硫辛酸可显著改善线粒体结构/功能,并建议在治疗中与具有协同自由基清除特性的生育酚(CAS 10191-41-0)联合使用。