THE EFFECT OF MEXIDOL ON GLUTATHIONE SYSTEM IN RAT BRAIN UNDER MODELING OF PARKINSON’S DESEASE

Abstract

We studied the effects of mexidol (3-oxy-6-methyl-2-ethylpiridine succinate) on the antioxidant glutathione system in rat brain mitochondria in experimental Parkinson’s disease induced by rotenone administration. Wistar rats were divided into the following groups of 6 in each: I - intact rats (control); II - rotenone (3 mg/kg per day) was injected subcutaneously for 2 weeks; III - after rotenone intoxication, mexidol (50 mg/kg per day) was injected intraperitoneally for 2 weeks. In the suspension of brain mitochondria, the activity of NADH dehydrogenase (complex I of the mitochondrial respiratory chain), content of the active products of 2-thiobarbituric acid (TBA-AP), the reduced (GSH) and oxidized (GSSG) glutathione amounts, the activity of glutathione-dependent enzymes: glutathione peroxidase (GP) and glutathione reductase (GR) as well as NADH+-isocitrate-dehydrogenase activity (NADPH+- ICDH) were measured. The activity and protein expression of MnSOD and GP in rat brain mitochondria were estimated. Treatment of rats with mexidol led to a weakening of oxidative processes in brain mitochondria in comparison with rats exposed to rotenone intoxication. It was shown that intraperitoneal injections of mexidol led to a decrease in the TBA-AP and in the GSSG content and to an increase in GSH/GSSG ratio in comparison with rotenone intoxication. It was also registered an increase in the activity of NADH-dehydrogenase. Such changes indicated a weakening of the mitochondrial oxidative processes intensity. Treatment of rats with mexidol promoted an increase in GSH content, GR and NADPH+-ICDH activities in brain mitochondria in comparison with rotenone administration. Treatment with mexidol resulted to an increased activity and protein expression of GP and MnSOD. We conclude that mexidol reduced the rotenone-induced damage of rat brain mitochondria increasing the action of glutathione-dependent and NADPH+-generating enzymes.