Vitamin D(3) contribution to the regulation of oxidative metabolism in the liver of diabetic mice

摘要

This work is devoted to the study of the features of oxidative metabolism of hepatocytes in diabetic mice and those under the vitamin Dsub3/sub action. We found out that a 2.5-fold decrease of 25OHDsub3/sub content in the serum was caused by chronic hyperglycemia in diabetes. Intensification of the reactive oxygen species (ROS) and nitrogen monoxide (NO) production, protein oxidative modifications (detected by the contents of carbonyl groups and 3-nitrotyrosine), accumulation of diene conjugates and TBA-reactive products of lipid peroxidation, and the decreased level of free SH-groups of low molecular weight compounds in the liver were accompanied by development of vitamin Dsub3/sub deficient state. It was shown that there was a decrease in the key antioxidant enzymes activity (catalase, SOD), while the activity of prooxidant enzymes NAD(P)H:quinone oxidoreductase, xanthine oxidase and NAD(P)H oxidase was increased. The identified oxidative metabolism lesions caused the elevation of the hepatocytes necrotic death that was tested for the ability of their nuclei to accumulate propidium iodide. Prolonged vitamin Dsub3/sub administration (during 2 months) at a dose of 20 IU to diabetic mice helps to reduce the ROS formation and biomacromolecules oxidative damage, normalizes the antioxidant system state in the liver and increases survival of hepatocytes. The results suggest that vitamin Dsub3/sub is a key player in the regulation of the oxidative metabolism in diabetes.