Statins are used to treat hypercholesterolemia, with several pleiotropic effects. Alongside their positive effects (for example, decreasing blood pressure), they can also bring about negative effects/symptoms (such as myopathy). Their main mechanism of action is inducing apoptosis, the key step being the release of cytochrome c from the mitochondria. This can be facilitated by oxidative stress, through which glutathione is oxidized. In this research, glutathione was used as a respiratory substrate to measure the mitochondrial oxygen consumption of rat liver with an O2 electrode. The reduction of cytochrome c was monitored photometrically. Hydrophilic (pravastatin) and lipophilic (simvastatin) statins were used for the measurements. Pravastatin reduces the reduction of cytochrome c and the oxygen consumption of the mitochondria, while simvastatin, on the other hand, increases the reduction of cytochrome c and the mitochondrial oxygen consumption. The results make it seem probable that statins influence the mitochondrial oxygen consumption through cytochrome c. Simvastatin could enhance the oxidizing capacity of free cytochrome c, thereby increasing oxidative stress and thus facilitating apoptosis. The observed effects could further the understanding of the mechanism of action of statins and thereby aid in constructing optimal statin therapy for every patient.
Keywords: apoptosis; cytochrome c; hypercholesterolemia; mitochondrial oxygen consumption; preeclampsia; statins.