Mitochondrial Oxidative Stress and Calcium-Dependent Permeability Transition are Key Players in the Mechanisms of Statins-Associated Side Effects

Abstract

Statins are cholesterol-lowering medicines utilized worldwide and are associated with reduced risk of cardiovascular mortality and events. However, 0.5-10% of patients suffer from adverse effects especially on skeletal muscle. Recently, new onset of diabetes has been reported in subjects on statin therapy. Pro-and anti-oxidant effects of statins have been reported, thus fostering a debate. Previously reported data provide evidence that statins induce alterations in intracellular calcium homeostasis and mitochondrial dysfunctions that can be counteracted by antioxidants (e.g., CoQ10, creatine, and L-carnitine). Therefore, we have proposed that statin-induced inhibition of mitochondrial respiration leads to oxidative stress that opens a calcium-dependent permeability transition pore, an event that may lead to cell death. In addition, mitochondrial oxidative stress caused by statin treatment may be a signal for cellular antioxidant system responses such as catalase upregulation, possibly explaining the alleged statins' antioxidant properties. Muscle mitochondrial dysfunction induced by statin treatment may be associated with the peripheral insulin resistance and may explain statins-induced new onset of diabetes. Together, the data presented in this review suggest that the statins' detrimental effects can be prevented by co-administration of antioxidants.

Statin-induced Liver Injury Patterns: A Clinical Review

“…1). 48 Genetic factors may affect patient susceptibility to liver injury in the setting of statin use. 49 A recent genome-wide association study identified transporter genes, cytochrome P450, organic anion-transporting polypeptides, and ATPbinding cassette genes ABCB1 and ABCC1 as possibly predisposing patients to statin-induced liver injury.…”