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 mi...

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Bibliographic Details
Published in:Toxicology and applied pharmacology 2007-09, Vol.223 (2), p.173-179
Main Authors: Tavintharan, S., Ong, C.N., Jeyaseelan, K., Sivakumar, M., Lim, S.C., Sum, C.F.
Format: Article
Language:English
Subjects:
60 APPLIED LIFE SCIENCES
Adenosine Triphosphate - metabolism
Analysis of Variance
APOPTOSIS
ATP
Biological and medical sciences
BROMIDES
CATTLE
Cell Line, Tumor
Cell Nucleus - drug effects
Cell Nucleus - metabolism
Cell Survival - drug effects
CHOLESTEROL
Chromatography, High Pressure Liquid
Coenzymes - metabolism
Coenzymes - pharmacology
DMSO
DNA
DNA Damage
Dose-Response Relationship, Drug
Hepatotoxicity
HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology
LIPOPROTEINS
Liver - drug effects
Liver - metabolism
Liver - pathology
Medical sciences
MITOCHONDRIA
Mitochondria - drug effects
Mitochondria - metabolism
OXIDATION
Oxidative stress
Oxidative Stress - drug effects
Simvastatin - pharmacology
Statins
Toxicology
Transaminitis
UBIQUINONE
Ubiquinone - analogs & derivatives
Ubiquinone - metabolism
Ubiquinone - pharmacology
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Summary: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.
ISSN:0041-008X
1096-0333
DOI:10.1016/j.taap.2007.05.013