Amine oxidases as important agents of pathological processes of rhabdomyolysis in rats.

In this study we have tested an idea on the important role of amine oxidases (semicarbazide-sensitive amine oxidase, diamine oxidase, polyamine oxidase) as an additional source of oxidative/carbonyl stress under glycerol-induced rhabdomyolysis, since the enhanced formation of reactive oxygen species and reactive carbonyl species in a variety of tissues is linked to various diseases. In our experiments we used the sensitive fluorescent method devised for estimation of amine oxidases activity in the rat kidney and thymus as targeted organs under rhabdomyolysis. We have found in vivo the multiple rises in activity of semicarbazide-sensitive amine oxidase, diamine oxidase, polyamine oxidase (2-4.5 times) in the corresponding cell fractions, whole cells or their lysates at the 3-6th day after glycerol injection. Aberrant antioxidant activities depended on rhabdomyolysis stage and had organ specificity. Additional treatment of animals with metal chelator 'Unithiol' adjusted only the activity of antioxidant enzymes but not amine oxidases in both organs. Furthermore the in vitro experiment showed that Fenton reaction (hydrogen peroxide in the presence of iron) products alone had no effect on semicarbazide-sensitive amine oxidase activity in rat liver cell fraction whereas supplementation with methylglyoxal resulted in its significant 2.5-fold enhancement. Combined action of the both agents had additive effect on semicarbazide-sensitive amine oxidase activity. We can assume that biogenic amine and polyamine catabolism by amine oxidases is upregulated by oxidative and carbonyl stress factors directly under rhabdomyolysis progression, and the increase in catabolic products concentration contributes to tissue damage in glycerol-induced acute renal failure and apoptosis stimulation in thymus.

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 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 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.