Experimental assessment of carbacetam effect on the cerebral mitochondria in rats with scopolamine-induced Alzheimer’s disease

• Main Authors: Olga G. KMET, Nataliia D. FILIPETS, Iryna M. YAREMII, Taras I. KMET, Yurii M. VEPRIUK, Tamara I. HRACHOVA
• Format: Article
• Language: English
• Published: Balkan Medical Union 2020-03-01
• Series: Archives of the Balkan Medical Union
• Subjects: carbacetam; scopolamine-induced alzheimer’s disease; functional state of the mitochondria
• Online Access: https://umbalk.org/wp-content/uploads/2020/03/01.EXPERIMENTAL-ASSESSMENT-OF-CARBACETAM-EFFECT.pdf

Introduction. One of the pathogenic chains in neurodegenerative diseases, and the Alzheimer’s disease especially, is the disorder of cellular energy supply. Investigation of changes in the indices characterizing a functional state of the mitochondria in the cerebral cortex and hippocampus under the influence of carbacetam, a new modulator of GABA-system, is of a certain interest. The objective of the study was to evaluate the protective effect of carbacetam under conditions of mitochondrial dysfunction of the brain in rats with scopolamine-induced Alzheimer’s disease. Materials and methods. The experiments were conducted on laboratory nonlinear albino male rats with the body weight of 0.18-0.20 kg. To simulate Alzheimer’s disease, scopolamine hydrochloride (Sigma, USA) was injected in rats through the peritoneum, in the dose of 1 mg/kg for 27 days. Since the 28th day of the experiment, carbacetam was introduced through the peritoneum in the dose of 5 mg/kg, in 1 mL of 0.9 % NaCl solution, once a day for 14 days. Results. Under conditions of scopolamine-induced Alzheimer’s disease, light dispersion decreases and a relative rate of mitochondrial swelling increases in the mitochondrial fraction of the cerebral cortex and hippocampus of rats; free radical oxidation of lipids and proteins increases, and activity of Krebs cycle enzymes decreases – -ketoglutarate dehydrogenase and succinate dehydrogenase. After carbacetam administration for 14 days, a gradual decrease of light dispersion and relative rate of mitochondrial swelling are found in the mitochondrial fraction of the cerebral cortex and hippocampus. Moreover, the content of products reacting with 2-thiobarbituric acid and protein oxidation modification in the examined structures decreases; the activity of catalase, -ketoglutarate dehydrogenase, succinate dehydrogenase increases, and superoxide dismutase – only in the cerebral cortex Conclusions. Reduced intensity of mitochondrial swelling, improvement of the antioxidant system state and energy supply of mitochondria in the cerebral cortex and hippocampus of rats with scopolamine-induced Alzheimer’s disease are indicative of mitoprotective properties of carbacetam as a promising neuroprotector.