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.
