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 (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.
Tavintharan
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Department of Medicine, Alexandra Hospital, and Department of Community, Occupational and Family Medicine, Yong Loo Lin School of Medicine, Singapore. tavintharan_subramaniam@alexhosp.com.sg
Ong
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CN
Jeyaseelan
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K
Sivakumar
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Lim
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Sum
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D000255:Adenosine Triphosphate / Q000378:metabolism; D000704:Analysis of Variance; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D003067:Coenzymes / Q000378:metabolism / Q000494:pharmacology; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D019821:Simvastatin / Q000494:pharmacology*; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology
D003067:Coenzymes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D014451:Ubiquinone; D000255:Adenosine Triphosphate; D019821:Simvastatin; C024989:coenzyme Q10