Keywords
Abstract
Diabetes mellitus (DM) is an importance medico-social problem. Almost 80 % of patients with diabetes have diabetic encephalopathy (DE) which leads to a significant impairment in the quality of life. Oxidative stress (OS) is considered to be a major factor in the development of DE in type 1 diabetes (DM1). Thus, hyperglycemia-induced OS causes excessive formation of reactive oxygen species and depletion of the antioxidant protection system which lead to energy depletion and, as a result, neuronal damage and death. Therefore, OS correction is considered to be one of the most promising areas of cerebroprotection in DM1. The purpose of the study was to investigate the effect of N-acetylcysteine (NAC), melatonin (Mel) and their combination on the state of mitochondrial electron transport chain (ETC) and antioxidant (AO) system in rats` brain with experimental DM1 Experiments were carried out on male Wistar rats. DM1 was induced by administration of streptozotocin (STZ). Rats with induced DM1 received NAC (1500 mg/kg), Mel (10 mg/kg) and their combination during 5 weeks, starting at 15 days after control pathology (CP) was reproduced. According to the results of experimental studies, obtained in the rats` with DM1 model, disruption of mitochondrial ETC in brain cells was detected. Thus, it was found a significant decrease of sulfur-iron proteins in 4,6-times (p <0,05) and ubiquinone radicals in 2,5-times (p < 0,05), while the level of iron nitrosol complexes was increased in 1,2-times (p < 0,05) to intact control values. The combined effect of NAC and Mel in rats with streptozotocin DM1 prevented the decreasing in the level of sulfur-iron proteins and ubiquinone radicals (by 2,0-times compared with control pathology group, p < 0,05, contributing to the normalization of mitochondrial ETC and thereby exhibiting antioxidant and antiapoptotic effects in brain cells. Joint use of the NAC and Mel showed the best antiradical effect reducing superoxide radicals generation by 1,7-times (p < 0,05). An increase of NO level by 2,0-times (p < 0,05) indicates the endothelial protective effect of this medicines combination and. may be associated with a normalization of endothelial NO synthase activity. Monotherapy of NAC and Mel was more effective in the final stages of OS. In particular, the administration of NAC was accompanied with increasing of the reduced glutathione level by 1,8-times (p < 0,05), whereas melatonin led to increase of catalase activity by 1,6-times (p < 0,05) versus CP group. These medicines, especially in combination, normalized the AO system indices in the blood of rats with DM1, as evidenced by the approximation of transferrin, ceruloplasmin, and methemoglobin levels (p < 0,05) to intact control values.