Reduced mitochondrial coenzyme Q10 levels in HepG2 cells treated with high-dose simvastatin: A possible role in statin-induced hepatotoxicity?
Tavintharan, S. ; Lim, S.C. ; Ong, C.N. ; Jeyaseelan, K. ; Sivakumar, M. ; Sum, C.F.
Tavintharan, S.
Lim, S.C.
Sivakumar, M.
Sum, C.F.
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Abstract
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 (CoQ10). In HepG2 cells, simvastatin decreased mitochondrial CoQ10 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 CoQ10, reduced cell death and DNA oxidative stress, and increased ATP synthesis. It is suggested that CoQ10 deficiency plays an important role in statin-induced hepatopathy, and that CoQ10 supplementation protects HepG2 cells from this complication. © 2007 Elsevier Inc. All rights reserved.
Keywords
Hepatotoxicity, Oxidative stress, Statins, Transaminitis, Ubiquinone
Source Title
Toxicology and Applied Pharmacology
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Series/Report No.
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Date
2007
DOI
Type
Article