Succinate dehydrogenase as a new target for melatonin binding in the complex diabetes mellitus treatment

Abstract

Relevance. Alloxan, destroying the beta cells of the pancreas, provokes hyperglycemia, which causes a hypoenergetic state. Mitochondrial succinate dehydrogenase dysfunction plays an important role in the pathogenesis of diabetes. Pharmacotherapy of diabetes mellitus has been and remains the subject of numerous studies. Recently, the attention of researchers is increasingly attracted by the hormone of the pineal gland - melatonin, due to its biological and pharmacological properties. The aim of the study was to study the effect of melatonin on the activity of succinate dehydrogenase as a new target in experimental alloxan-induced diabetes mellitus. Materials and methods. The studies were carried out on male Wistar rats, with an average mass of 120-150 g, which were kept on a standard diet. The animals were divided into 4 groups. The control group was injected with saline solution, the second group was injected with melatonin at a dose of 1 mg/kg daily for 14 days, experimental diabetes in animals was simulated by intraperitoneal administration of alloxan at a dose of 150 mg/kg with diabetes. The fourth group of animals received melatonin on the background of alloxan. Succinate dehydrogenase activity was determined in liver and pancreatic tissues by photometric method. For the docking analysis, the AutoDock Vina and AutoDock Tools software packages were used. Results and Discussion. According to the results obtained, reciprocal relationships arise under the influence of alloxan in the activity of SDH in the liver and pancreas. Alloxan causes an increase in the activity of SDH in the liver by 1.9 times, and in the pancreatic tissue there is a significant decrease - by 5 times. The use of melatonin for animals with alloxan diabetes led to a decrease in the activity of succinate dehydrogenase in the liver by one and a half times in comparison with the indicators of rats with alloxan diabetes. In the pancreas, on the contrary, the activity of the enzyme increased by 3.3 times, which may indicate the restoration of the function of Langerhans beta cells. Conclusion. Melatonin blocking succinate dehydrogenase domain A reduces the hyperactivity of the enzyme in the liver, and in the pancreas through its specific receptors (MR1 and MR2) present on the surface of the membranes of β- and α-cells directly interferes with the function of the cellular elements of the islets of Langerhans, restoring them.

Keywords

• diabetes
• melatonin
• succinate dehydrogenase (sdh)
• molecular docking