Protective Effects of Coenzyme Q10 on Decreased Oxidative Stress Resistance Induced by Simvastatin

• Published in: Journal of Clinical Biochemistry and Nutrition Vol. 40; no. 3; pp. 194 - 202
• Main Authors: Kettawan, Aikkarach, Takahashi, Takayuki, Kongkachuichai, Ratchanee, Charoenkiatkul, Somsri, Kishi, Takeo, Okamoto, Tadashi
• Format: Journal Article
• Language: English
• Published: Gifu SOCIETY FOR FREE RADICAL RESEARCH JAPAN 2007; Japan Science and Technology Agency; the Society for Free Radical Research Japan
• Subjects: coenzyme Q10; HMG-CoA reductase inhibitor; Original; oxidative stress; statin; ubiquinol-10
• ISSN: 0912-0009; 1880-5086
• DOI: 10.3164/jcbn.40.194

The effects of simvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl CoA reductase (HMG-CoA reductase), on oxidative stress resistance and the protective effects of coenzyme Q (CoQ) were investigated. When simvastatin was administered orally to mice, the levels of oxidized and reduced CoQ9 and CoQ10 in serum, liver, and heart, decreased significantly when compared to those of control. The levels of thiobarbituric acid reactive substances induced by Fe2+-ascorbate in liver and heart mitochondria also increased significantly with simvastatin. Furthermore, cultured cardiac myocytes treated with simvastatin exhibited less resistance to oxidative stress, decreased time to the cessation of spontaneous beating in response to H2O2 addition, and decreased responsiveness to electrical field stimulation. These results suggested that oral administration of simvastatin suppresses the biosynthesis of CoQ, which shares the same biosynthesis pathway as cholesterol up to farnesyl pyrophosphate, thus compromising the physiological function of reduced CoQ, which possesses antioxidant activity. However, these undesirable effects induced by simvastatin were alleviated by coadministering CoQ10 with simvastatin to mice. Simvastatin also reduced the activity of NADPH-CoQ reductase, a biological enzyme that converts oxidized CoQ to the corresponding reduced CoQ, while CoQ10 administration improved it. These findings may also support the efficacy of coadministering CoQ10 with statins.