Reduced mitochondrial coenzyme Q10 levels in HepG2 cells treated with high-dose simvastatin: A possible role in statin-induced hepatotoxicity?

Lowering of low-density lipoprotein cholesterol is well achieved by 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins). Statins inhibit the conversion of HMG-CoA to mevalonate, a precursor for cholesterol and coenzyme Q10 (CoQ(10)). In HepG2 cells, simvastatin decreased mitochondrial CoQ(10) levels, and at higher concentrations was associated with a moderately higher degree of cell death, increased DNA oxidative damage and a reduction in ATP synthesis. Supplementation of CoQ(10), reduced cell death and DNA oxidative stress, and increased ATP synthesis. It is suggested that CoQ(10) deficiency plays an important role in statin-induced hepatopathy, and that CoQ(10) supplementation protects HepG2 cells from this complication. (C) 2007 Elsevier Inc. All rights reserved.