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Abstract

Neurodegenerative disorders in the cerebral cortex and hippocampus are one of the most common causes of disability and mortality in patients with diabetes. Excessive glucose concentration causes a toxic effect due to an increased amount of glycolysis products, lipid and protein peroxide oxidation, decreased membranous potential of the mitochondria and deficiency of neuron energy supply due to mitochondrial dysfunction. Gammaamino butyric acid is known to localize to the mitochondria, and its functional cycle is closely linked to glucose metabolism. Objective of the study: experimental investigation of сarbacetam effect with cerebral mitochondrial dysfunction of rats with type 2 diabetes mellitus. The experiments were conducted on laboratory nonlinear albino male rats with the body weight 0.18–0.20 kg. Type 2 diabetes is modeled on streptozotocin and a high-fat diet. Carbacetam was administered intraperitoneally at a dose of 5 mg/kg, once daily for 14 days. Under conditions of central nervous system damage induced by type 2 diabetes mellitus, lipid and protein peroxide oxidation increases in the mitochondrial fraction of the cerebral cortex and hippocampus of rats; activity of superoxide dismutase, catalase, α-ketoglutarate dehydrogenase, succinate dehydrogenase decreases; a relative rate of mitochondrial swelling increases. After carbacetam administration during 14 days the content of products reacting with 2-thiobarbituric acid and protein oxidation modification decrease in the mitochondria of the brain and hippocampus of rats with type 2 diabetes mellitus; activity of catalase in the cerebral cortex and α-ketoglutarate dehydrogenase in the hippocampus increases, activity of succinate dehydrogenase increases in both structures examined which is indicative of its antioxidant properties. Decrease of a relative rate of mitochondrial swelling in the cerebral cortex and hippocampus of rats confirms a protective effect of carbacetam under conditions of mitochondrial dysfunction.