State of peroxidation in the brain and liver in experimental diabetes and its correction possibility with niacin-oxyethylendiphosphonatogermanate

Abstract

The development of pharmacological methods to control oxidant stress manifestations in diabetes can be achieved using organic complex germanium compounds. One of the promising compounds is niacin-oxyethylenediphosphonategermanate (MIGU-4), which is an effective corrector of lipid metabolism and a stabilizer of the lipid layer of erythrocyte and hepatocyte membranes in the streptozotocin-induced diabetic model. The aim of the work is to determine the dynamics of the malondialdehyde (MDA) content, the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPO) in the brain tissue, as well as the diene conjugate (DC) content, lipid hydroperoxides (LHP), reduced glutathione (GSH) in the liver mitochondria, the serum activities of aspartate and alanine aminotransferases (AST and ALT) in experimental diabetes mellitus with the correction using a complex compound of germanium with nicotinic acid – MIGU-4 and insulin, insulin alone as well as in comparison with effectiveness of vitamin E supplementation. Materials and methods. Diabetes was induced in male Wistar rats by intraperitoneal injection of streptozotocin (60.0 mg/kg). MIGU-4 was administered intraperitoneally at a dose of ED50 that was 25.0 mg/kg. Mitochondrial membranes were obtained by differential centrifugation of the liver tissue. In rats with confirmed diabetes, parameters of peroxidation and antioxidant protection were studied by generally accepted biochemical and biophysical methods. Results. Glucose levels were 29.4 % lower in rats treated with MIGU-4 (25.0 mg/kg) after 8 weeks of streptozotocin-induced diabetes than those in untreated diabetic rats (p < 0.05), while a decrease was 39.0 % (p < 0.05) upon insulin treatment, and 47.2 % (p < 0.05) – with combined use of the drugs. The MDA content in the brain tissue was 3.48 times higher than that in the control (p < 0.05). At the same time, the activities of SOD and CAT were decreased by 46.4 % and 32.0 %, respectively, the activity of GPO was decreased by half (p < 0.05). In the liver mitochondria, the DC content exceeded that in the control by 53.5 % (p < 0.05), and the MDA and LHP levels were 2.48 times and 31.7 % higher (p < 0.05), respectively. AST activity was almost doubled, ALT activity was 5.48 times increased. Insulin and the biologically active substance MIGU-4 used alone exerted a moderate corrective effect. The combined use of the drugs caused definite therapeutic and preventive effects as the brain content of MDA was 2.4 times decreased, the activity of SOD, CAT and GPO was increased by 45.6 %, 35.2 % and 67.3 % (p < 0.05), respectively. In the liver mitochondria, the DC, MDA, and LHP contents were decreased by 41.0 %, 53.3 %, and 28.4 %, respectively, compared to those in rats with diabetes (p < 0.05). The activity of SOD and CAT as well as GSH content were increased by 2.7 times, 51.9 %, and 23.0 % (p < 0.05), respectively. AST and ALT activities were 42.2 % and 74.3 % (p < 0.05) reduced, respectively. The combined use of MIGU-4 (25.0 mg/kg) and vitamin E (250.0 mg/kg) caused a decrease in the brain MDA content by 70.1 % (p < 0.05) in experimental rats. The combination of MIGU-4 and vitamin E increased the activity of GPO by 58.3 % (p < 0.05) as compared to rats with diabetes, indicating cumulative effects of these drugs. Conclusions. The use of MIGU-4 prevents the occurrence of oxidant stress manifestations in the brain tissue and liver mitochondria in streptozotocin-induced diabetes. The corrective effect size of MIGU-4 (25.0 mg/kg) corresponds to that of vitamin E (250.0 mg/kg).