N-acetylcysteinate 2-ethyl-6-methyl-3-hydroxypiridine increases the body’s resistance to acute hypobaric hypoxia
Emanuel Institute of Biochemical Physics Russian Academy of Sciences, st. Kosygin 4, Moscow, 119334 Russia, tel. +79495)-939-74-09
Mitochondria occupy key positions in energy, redox and metabolic processes in the cell. However, in the conditions of stress, these organelles are one of the main sources of active oxygen species (ROS) [Todorov I.N., 2007],. Excessive generation of ROS leads to peroxidation of membrane lipids, primarily cardiolipin, and swelling of mitochondria. The consequence of the" peroxide " swelling of mitochondria (or the formation of large pores in the outer membrane) is the release of apoptogenic proteins from the intermembrane space into the cytoplasm and the activation of the mitochondrial pathway of apoptosis.
It can be assumed, that drugs that reduce the generation of ROS by mitochondria will increase the body's resistance to the action of stress factors, in particular, to acute hypobaric hypoxia (AHH). As such preparations, antioxidants, in particular N-acetylcysteinate 2-ethyl-6-methyl-3-hydroxypyridine (3-HP), can probably be used. Since energy metabolism is a target for hypoxia and one of the first among other metabolic processes is disturbed under conditions of oxygen deficiency [Lukyanova L.D., Vlasova I.G., 1991] it was interesting to find out how AHH and 3-HP influence the functional characteristics of rat liver mitochondria. In this case, the respiration rate of mitochondria was studied using the polarographic method and the fatty acid composition of the lipids of the membranes of these organelles was determined by gas-liquid chromatography
AHH, activating lipid peroxidation, reduces the content of unsaturated fatty acids (fatty acids) with 18 carbon atoms in the membranes of rat liver mitochondria. The index of double bonds of FA, containing 18 carbon atoms, decreased from 1.40 ± 0.02 to 1.10 ± 0.01. This process is accompanied by a decrease in the maximum oxidation rates of the NAD-dependent substrates. At the same time, the efficiency of oxidative phosphorylation decreased. However, the rate of succinate oxidation even slightly increased in the presence of ADP.
Injection to rats 10-8 M 3-HP 45 minutes before exposure prevented changes in the functional characteristics of liver mitochondria: the maximum oxidation rates of the NAD-dependent substrates and succinate did not differ from the control values, which indicated that the drug corrected the functional characteristics of mitochondria. Indeed, it is known that the restoration of the rates of oxidation of NAD-dependent substrates by mitochondria is important in the formation of resistance to hypoxia [Nikonov VV, Pavlenko A.Yu., 2009].