Ambiol Prevents Changes in the Functional Characteristics of Mitochondria Under Hypoxia

Oxidative stress occurs when there is an excess of reactive oxygen species (ROS) in the cell, primarily produced by mitochondria. Excess ROS trigger membrane lipid peroxidation (LPO), cause mitochondrial swelling, and release proapoptotic proteins into the cytoplasm, which can lead to apoptosis. It is assumed that antioxidants that reduce excessive ROS formation by mitochondria can increase the body's resistance to stress factors. We investigated the effects of hypoxia and the antioxidant Ambiol (2-methyl-4-dimethylaminomethylbenzimidazole-5-ol dihydrochloride) on the functional characteristics of mitochondria, which were assessed by measuring lipid peroxidation intensity using spectrofluorimetry, mitochondrial membranes fatty acid composition using chromatography, mitochondrial morphology using atomic force microscopy, and respiration rate using polarography. Injecting mice with Ambiol at a dose of 10^-6 mol/kg for 5 days prevented the stress-induced activation of lipid peroxidation, a decrease in the unsaturation index of C₁₈ and C₂₀ fatty acids in mitochondrial membranes, and swelling of these organelles. The drug also increased the efficiency of oxidative phosphorylation during the oxidation of NAD-dependent substrates. Furthermore, Ambiol increased the lifespan of mice by 3.0-4.0 times under various types of hypoxia. Ambiol's ability to maintain initial (control) levels of C₁₈ and C₂₀ unsaturated fatty acids appears to protect against stress-induced mitochondrial dysfunction.