LAPROXIDE EFFECT ON ENERGY METABOLISM DISORDERS IN SUB-TOXIC DOSES WITH LONG INTAKE OF WARM-BLOODED ANIMALS

In subacute experiment (45 days) with white rats (n=50) it was modeled intoxication with laproxides L-500 and L-303 in a dose of 1/100 and 1/1000 LD50. The control group (n=10) were administered the same volume of drinking water.

The purpose of the study. There was examined the metabolic state of mitochondria and oxidant-antioxidant status interaction at long intake of organism under the influence of subtoxic laproxides.

Materials and methods. There were determined the state of oxidant-antioxidant homeostasis, tissue respiration and oxidative phosphorylation, AMP and content-rich compounds (ATP, ADP), inorganic phosphate, cyclic guanosine monophosphate (cGMP), malonic dialdegides (MDA), diene conjugates (DC), catalase activity, ceruloplasmin (CPU) and superoxide dismutase (SOD).

Results and discussion. There was revealed a significant decrease in mitochondrial respiration after the addition of succinate (V4), substrate phosphorylation — ADP (V3), and after making uncoupler — 2,4-DNP (V4′) as well as lower respiratory gain, phosphorylation, as well as activity Ca2+-, Mg2+-dependent ATP-ase inhibition on background ATP hydrolase reaction under the influence of 1/100 LD50. At a dose of 1/1000 LD50 investigated xenobiotics have not changed metabolic state of mitochondria in comparison with control. The analysis indicates that xenobiotics in 1/100 LD50 can stimulate free radical processes, lipid peroxidation and oxidative modification of proteins.

Findings. Thus, research results provide a basis to judge that laproxides at a dose of 1/100 LD50 were able to activate free radical processes, lipid peroxidation, oxidative modification of proteins, which lead to the inhibition of tissue respiration, oxidative phosphorylation and synthesis of high-energy compounds that involve tissue hypoxia and rehabilitation synthesis suppression.