Neuroprotective Activity of 5-ethoxy-2-ethylthiobenzimidazole (Etomerzol) and 2-ethylthiobenzimidazole (Bemitil) in a Model of Middle Cerebral Artery Occlusion

Abstract

Introduction. Cerebrovascular diseases (CVD) are one of the most pressing medical and social problems due to the high rate of mortality and disability. Stroke is the leading cause of CVD. About 15 million strokes are registered annually in the world according to the World Federation of Neurological Societies. It should be noted that CVD of ischemic origin has a tendency to rejuvenation and growth. Traditionally, in clinical practice, antihypoxic, antioxidant agents, as well as drugs with neuroprotective and neurorehabilitation effects are used to treat CVD. In connection with the increase in the incidence of CVD, there is an urgent need to search for promising neuroprotectors.Aim. To study the neuroprotective activity of 5-ethoxy-2-ethylthiobenzimidazole (etomerzol) and 2-ethylthiobenzimidazole (bemityl) in a model of middle cerebral artery occlusion.Materials and methods. Occlusion of the middle cerebral artery (ОMCA) was used as a model. The object of the study was inbred male rats of the Dark Agouti line, randomized into five groups: a group of intact animals and four groups with OSMA: a control group, a group with the introduction of 5-ethoxy-2-ethylthiobenzimidazole (etomerzole, 25 mg/kg), a group with the introduction 2-ethylthiobenzimidazole (bemityl, 25 mg/kg) and a group with the reference drug dimethyl fumarate (DMF, 100 mg/kg). On the 1st, 3rd, and 7th days after the operation, the "Limb Stimulation" (SC) test was performed. On the 7th day, the tests "Open field" (OP) and "Elevated plus maze" (EPM) were performed. Euthanasia was performed on the 7th day in an induction chamber (Bioscape GmbH, CO2 box for euthanasia, Germany).Results and discussion. The study showed a pronounced pharmacological effect of etomerzole in a model of acute ischemic stroke. The introduction of bemitil, etomerzol and DMF significantly reduced the neurological deficit 24 hours after OSMA and improved the psycho-functional state on the 7th day. Thus, in the etomerzol group on the first day after surgery, the neurological deficit was reduced by 1.9 times (p < 0.05), and by 3 and 2.0 times (p < 0.05) compared with the control group. While bemityl and DMF reduced the index by 1.3 (p < 0.05) and 1.4 times (p < 0.05) on the 3rd day and by 1.5 times (p < 0.05) on the 7th day. In the OP test in the etomerzol group, an increase in HDA by 2.7 times (p < 0.05) was observed compared with the control. The rate of peering into minks in the etomersol and bemitil groups was higher than in the control group by 2.6 (p < 0.05) and 3.4 times (p < 0.05), respectively. Search and research activity was increased in the same groups by 2.0 (p < 0.05) and 2.2 times (p < 0.05) compared to control animals. In the PCL test, the etomerzol and DMF groups showed an increase in the number of uprights in the sleeves compared to the control group by 2.7 (p < 0.05) and 3.8 times (p < 0.05), respectively. In the etomerzol and bemityl groups, there was an increase in the number of overhangs by 3.4 (p < 0.05) and 6.2 times (p < 0.05).Conclusion. The data obtained during the study of the activity of benzimidazoles after ischemic stroke indicate a significant increase in the motor activity of animals in the OP tests, which may indicate a psychostimulating and potential nootropic effect of etomerzole and bemitil, and an increase in the number of racks and hangings in the PCL test can be regarded as manifestation of anxiolytic activity. In our study, the severity of the pharmacological effects of DMF was inferior to benzimidazoles. However, a significant decrease in neurological deficit in the SC test and an increase in the number of uprights in the sleeves in the PCL may indicate the presence of anxiolytic activity in the drug. The results obtained underline the importance of conducting additional studies to evaluate the effectiveness of DMF in OSMA.