Mitochondrial cerebral dysfunction in rats with scopolamine-induced neurodegeneration under enalapril effect

Abstract

Objective. Neurodestructive diseases are characterized by complex pathobiochemical cascades in the neuron, which cause disturbances in energy metabolism and the formation of mitochondrial dysfunction. The renin-angiotensin system plays an important role in the physiological functioning of mitochondria, the excessive activity of which increases the risk of neurodegenerative diseases of the brain. Although angiotensin-converting enzyme inhibitors are now considered as means of prevention and treatment of ischemic lesions of the central nervous system, their corrective properties in the development of central neurodegeneration continue to be refined. The objective of our study was investigation of enalapril effect, as an angiotensin-converting enzyme inhibitor, in case of mitochondrial dysfunction of the cerebral cortex and hippocampus of rats under conditions of scopolamine-induced neurodegeneration reproducing development of Alzheimer’s disease in the experiment.Material and methods. Scopolamine hydrochloride (Sigma, USA) was injected in rats through the peritoneum at a dose of 1 mg/kg for 27 days to simulate Alzheimer’s disease. Starting from the 28th day of the experiment, enalapril was introduced through the peritoneum at a dose of 1 mg/kg, once a day for 14 days.
 Results. Under conditions of scopolamine-induced Alzheimer’s disease in the mitochondrial fraction of the cerebral cortex and hippocampus of rats free radical oxidation of lipids and proteins ncreases, and activity of Krebs cycle enzymes decreases – α-ketoglutarate dehydrogenase and succinate dehydrogenase; light dispersion decreases and a relative rate of mitochondrial swelling increases. After enalapril administration for 14 days to rats with scopolamine-induced Alzheimer’s disease the content of products reacting with 2-thiobarbituric acid and protein oxidation modification decreases in the mitochondrial fraction of the cerebral cortex and hippocampus; in both examined structures, the activity of catalase, αketoglutarate dehydrogenase, succinate dehydrogenase increases, and superoxide dismutase – only in the cerebral cortex; a gradual decrease of light dispersion and relative rate of mitochondrial swelling occurs.Conclusion. Improvement of the antioxidant system state and energy supply of mitochondria, decreased intensity of mitochondrial swelling in the cerebral cortex and hippocampus of rats with scopolamine-induced Alzheimer’s disease are indicative of the protective properties of enalapril.