VITAMIN D3 CONTRIBUTION TO THE REGULATION OF OXIDATIVE METABOLISM IN THE LIVER OF DIABETIC MICE.
This work is devoted to the study of the features of oxidative metabolism of hepatocytes in diabetic mice and those under the vitamin D3 action. We found out that a 2.5-fold decrease of 25OHD3 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 D3 deficient state. It was shown that there was a decrease in the key antioxidant enzymes activity (catalase, SOD), while the activity of prooxidant enzymes
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 D3 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 D3 is a key player in the regulation of the oxidative metabolism in diabetes.
D O
DO
Labudzynskyi
O V
OV
Zaitseva
N V
NV
Latyshko
O O
OO
Gudkova
M M
MM
Veliky
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002762:Cholecalciferol / Q000378:metabolism* / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D003922:Diabetes Mellitus, Type 1 / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D022781:Hepatocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008815:Mice, Inbred Strains; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism
D000975:Antioxidants; D017382:Reactive Oxygen Species; D002762:Cholecalciferol