10-(6′-Plastoquinonyl)decyltriphenylphosphonium (SkQ1) Does Not Increase the Level of Cytochromes P450 in Rat Liver and Human Hepatocyte Cell Culture

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K. N. Myasoedova^1,2*, D. N. Silachev^2,3, and A. D. Petrov⁴

¹Lomonosov Moscow State University, Faculty of Fundamental Medicine, 119991 Moscow, Russia; E-mail: skulach@belozersky.msu.ru

²Lomonosov Moscow State University, Institute of Mitoengineering, 119991 Moscow, Russia

³Lomonosov Moscow State University, Belozersky Institute of Physico-Chemical Biology, 119991 Moscow, Russia

⁴Mitotech S.A., 42 rue de la Vallee, Luxembourg L-2661, Luxembourg; E-mail: antonp@mitotechpharma.com

^* To whom correspondence should be addressed.

Received September 16, 2016

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Mitochondria-targeted antioxidant SkQ1 did not increase the content of cytochromes P450 in livers of rats that were given SkQ1 in drinking water for 5 days in a dose (2.5 µmol per kg body weight) that exceeded 10 times the SkQ1 therapeutic dose. SkQ1 did not affect the levels of cytochrome P450 forms CYP1A2, CYP2B6, and CYP3A4 in monolayer cultures of freshly isolated human hepatocytes, while specific inducers of these forms (omeprazole, phenobarbital, and rifampicin, respectively) significantly increased expression of the cytochromes P450 under the same conditions. We conclude that therapeutic doses of SkQ1 do not induce cytochromes P450 in liver, and the absence of the inducing effect cannot be explained by poor availability of hepatocytes to SkQ1 in vivo.

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KEY WORDS: cytochrome P450, SkQ1, mitochondria-targeted antioxidant, hepatocyte culture

DOI: 10.1134/S0006297916120105

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