title en

Journal archive > 2014 > N 5 September-October

THE ROS-GENERATING AND ANTIOXIDANT SYSTEMS IN THE LIVER OF RATS
TREATED WITH PREDNISOLONE AND VITAMIN D3

I. O. Shymanskyy, A. V. Khomenko, O. O. Lisakovska, D. O. Labudzynskyi, L. I. Apukhovska, M. M. Veliky

Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;

The mechanisms of glucocorticoid-induced disturbances of liver function is currently not fully clarified. Vitamin D3 was previously shown to play an important role in the regulation of impaired oxidative metabolism and detoxification function of the liver associated with the effects of hepatotoxic compounds. The study was undertaken to define the intensity of oxidative metabolism in the rat liver and survival of hepatocytes after prolonged prednisolone administration and to assess whether vitamin D3 is capable to counter glucocorticoid-induced changes. It has been shown that prednisolone (0.5 mg per animal for 30 days) leads to 1.6-fold increase in the percentage of necrotic cells among isolated hepatocytes as compared with the control. The glucocorticoid-induced impairment of hepatocellular function was accompanied by enhanced generation of reactive oxygen species (ROS), accumulation of TBA-active products and carbonylated proteins but reduced levels­ of free SH-groups of low molecular weight compounds. It was demonstrated a decrease in the activities of key enzymes of antioxidant system (SOD, catalase, glutathione peroxidase), whereas the activities of pro-oxidant enzymes NAD(P)H-quinone oxidoreductase and semicarbazide-sensitive amine oxidase were shown to be increased. Vitamin D3 (and to greater extent in combination with α-tocopherol) administration (100 IU) on the background of glucocorticoid therapy caused normalizing effects on the level of ROS formation, oxidative modification of biomolecules and activity of antioxidant enzymes resulting in better survival of hepatocytes. These data suggest a potential role of vitamin D3 in the regulation of oxidative metabolism alterations related to hepatotoxic action of glucocorticoids.

Key words: 25OHD3, prednisolone, reactive oxygen species, peroxide oxidation of biomolecules, pro- and antioxidant enzymes.

The original article in Ukrainian is available for download in PDF format.

© The Ukrainian Biochemical Journal