Abstract
Background: Stress factors lead to a shift in the antioxidant-prooxidant relationship, allowing an increase in the generation of reactive oxygen species (ROS) by mitochondria, which results in the development of oxidative stress. Consequently, it is possible to put forward an assumption that drugs which reduce the excessive generation of ROS by these organelles should increase the body's resistance to stress factors. Antioxidants can be used as such drugs. In this regard, the aim of this work was to study the bioenergetics characteristic of mitochondria under stress conditions and under the action of 2-ethyl-6-methyl-3-hydroxypyridinium hydroxybutanedioate (ethoxidol).
Methods: The antiradical activity of the drug was evaluated by the chemiluminescent method (CL). The functional state of the mitochondria was studied with reference to the level of lipid peroxidation by the spectrofluorimetry and in terms of fatty acid composition of mitochondrial membranes using the chromatography technique. The study of mitochondrial morphology was performed employing the method of atomic force microscopy.
Results: The injection in mice of ethoxidol at a dose of 10-5 mol/kg for 7 days led to the prevention of the stress-induced increase in the intensity of LPO in the membranes of the mitochondria, and swelling of these organelles; it also prevented a decrease in the content of unsaturated fatty acids, containing 18 and 20 carbon atoms. At the same time, ethoxidol increased the life expectancy of mice by 3.0-4.2 times in conditions of various types of hypoxia.
Conclusion: The adaptogenic properties of ethoxidol can be attributed to its antiradical and antioxidant properties.
Keywords: Mitochondria, LPO, antiradical activity, fatty acids, antioxidants, 3-hydroxypyridine, adaptogens.
Graphical Abstract
[http://dx.doi.org/10.1134/S0006297913130087] [PMID: 24490736]
[http://dx.doi.org/10.1155/2016/1245049] [PMID: 27478531]
[http://dx.doi.org/10.1016/j.freeradbiomed.2004.05.034] [PMID: 15304252]
[http://dx.doi.org/10.1139/cjz-2013-0131]
[http://dx.doi.org/10.1074/mcp.M400210-MCP200] [PMID: 15914488]
[http://dx.doi.org/10.1134/S0006297907100094] [PMID: 18021069]
[http://dx.doi.org/10.5152/eurasianjmed.2018.17397] [PMID: 30515042]
[PMID: 3522269]
[http://dx.doi.org/10.17691/stm2020.12.2.08] [PMID: 34513055]
[http://dx.doi.org/10.3390/antiox8020034] [PMID: 30717452 ]
[http://dx.doi.org/10.1016/0005-2728(78)90109-3] [PMID: 204343]
[http://dx.doi.org/10.1016/0003-2697(73)90327-8] [PMID: 4696687]
[http://dx.doi.org/10.1016/S0021-9673(00)88356-9]
[http://dx.doi.org/10.1093/ps/79.8.1168] [PMID: 10947186]
[http://dx.doi.org/10.1007/BF02262915]
[PMID: 16277217]
[http://dx.doi.org/10.1161/01.RES.0000109416.56608.64] [PMID: 14656928]
[http://dx.doi.org/10.1016/j.bbabio.2013.12.009] [PMID: 24368156]
[http://dx.doi.org/10.4161/psb.29228]
[http://dx.doi.org/10.3390/cells8070728] [PMID: 31315173]