Prevention of Mitochondrial Dysfunction with 2-Ethyl-6-Methyl-3-Hydroxypyridine Carnitinate

Abstract

The biological activity of 2-ethyl-6-methyl-3-hydroxypyridine carnitinate was studied. The drug showed high antiradical and antioxidant activity; this could indicate anti-stress properties, which were studied on a model of acute hypobaric hypoxia. Acute hypobaric hypoxia activated lipid peroxidation by 2.3 times, which resulted in changes in the content of C18 and C20 fatty acids in mitochondrial membranes; the index of double bonds of C18 fatty acids decreased by 18.2%, the content of 20:3ω3 by 13%, 20:2ω6 by 80% and 20:1ω9 by 33%. These changes were accompanied by changes in the bioenergetic characteristics of mitochondria. The maximum oxidation rates of NAD-dependent substrates decreased by 28–35%. The administration of 10^–6 mol/kg of 2-ethyl-6-methyl-3-hydroxypyridine carnitinate to animals for 5 days inhibited lipid peroxidation, prevented changes in the composition of fatty acids of mitochondrial membranes, and, consequently, changes in the bioenergetic characteristics of mitochondria; this probably determined the anti-stress properties of the drug, as indicated by an increase in life expectancy by 3.5–4.0 times and an increase in the survival rate of mice by 12–40% under conditions of various types of hypoxia. In addition, the drug stimulated the germination and growth of wheat seedlings.