2-ETHYL-6-METHYL-3-HYDROXYPYRIDINE CARNITINATEIS A BROAD-SPECTRUM ADAPTOGEN, THAT STIMULATES AUTOPHAGY IN LIVER TISSUE

Background: Under stress conditions, mitochondria become sources of excessive generation of reactive oxygen species (ROS), which can serve either as signaling molecules or damage cell structures. Antioxidants, reducing ROS generation, can serve as adaptogens to stress effects. It has been shown that a number of antioxidants are able to induce autophagy, which is able to activate the antioxidant-response element system. In this regard, the aim of the study was to investigate the anti-stress properties of a new antioxidant 2-ethyl-6-methyl-3-hydroxypyridine carnitinate (CP) and its ability to activate the synthesis of autophagy proteins Beclin-1, LC3. Methods: Since the body’s resistance to stress factors primarily depends on energy metabolism, the effects of acute hypobaric hypoxia and CP on the LPO intensity in the lipid fraction of mice liver mitochondrial membranes were studied using the spectrofluorescence method. Autophagy proteins were determined by Western blotting using primary mice antibodies to Beclin-1 and LС3B proteins, as well as secondary antibodies labeled with horseradish peroxidase. Results: Injection of 10-6 mol/kg CP to mice for 5 days prevented the growth of LPO intensity under conditions of acute hypobaric hypoxia (AHH). This drug increased life expectancy and increased survival of mice under conditions of various types of the hypoxia. The initiation of autophagy biomarker proteins (LC3B) by the drug was shown. At the same time, the content of Beclin-1 proteins tended to increase, which characterizes the onset of the autophagy process. Conclusion: The new antioxidant CP can probably be used as an adaptogen to various types of hypoxia and an activator of autophagy.