Tag Archives: prednisolone
Prednisolone and vitamin D(3) modulate oxidative metabolism and cell death pathways in blood and bone marrow mononuclear cells
I. O. Shymanskyy, O. O. Lisakovska, A. O. Mazanova,
D. O. Labudzynskyi, A. V. Khomenko, M. M. Veliky
Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
e-mail: ishymansk@inbox.ru
The study was designed to evaluate reactive oxygen species (ROS)/nitric oxide (NO) formation and apoptotic/necrotic cell death elicited by prednisolone in peripheral blood and bone marrow mononuclear cells and to define the efficacy of vitamin D3 to counter glucocorticoid (GC)-induced changes. It was shown that prednisolone (5 mg per kg of female Wistar rat’s body weight for 30 days) evoked ROS and NO overproduction by blood mononuclear cells (monocytes and lymphocytes) that correlated with increased cell apoptosis and necrosis. In contrast, prednisolone did not affect ROS/NO levels in bone marrow mononuclear cells that corresponded to lower level of cell death than in the control. Alterations of prooxidant processes revealed in mononuclear cells and associated with GC action were accompanied by vitamin D3 deficiency in animals, which was assessed by the decreased level of blood serum 25-hydroxivitamin D3 (25OHD3). Vitamin D3 administration (100 IU per rat daily for 30 days, concurrently with prednisolone administration) completely restored 25OHD3 content to the control values and significantly reversed ROS and NO formation in blood mononuclear cells, thus leading to decreased apoptosis. In bone marrow, vitamin D3 activated ROS/NO production and protein nitration that may play a role in prevention of prednisolone-elicited increase in bone resorption. We conclude that vitamin D3 shows a profound protection against GC-associated cellular damage through regulating intracellular ROS/NO formation and cell death pathways.
Cholecalciferol hydroxylation in rat hepatocytes under the influence of prednisolone
A. V. Khomenko
Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
e-mail: annavic@ukr.net
Glucocorticoid therapy is accompanied by development of processes typical of steroid osteoporosis. Indirect effects of glucocorticoids on the bone tissue are due to changes in mineral metabolism, which is regulated by vitamin D3. In this connection, we studied the influence of prednisolone on cholecalciferol metabolism. The study has shown that prednisolone action causes impairment of cholecalciferol metabolism in hepatocytes due to inhibiting vitamin D3 25-hydroxylase activity. Microsomal (CYP2R1) and mitochondrial (CYP27A1) isoenzymes of vitamin D3 25-hydroxylase were found to function at different concentrations of the substrate. The relative protein contents of the isoenzymes greatly differed in the liver with the prevalence of CYP27A1 over CYP2R1. Prednisolone administration resulted in the lowering of both mitochondrial and microsomal isoenzymes of vitamin D3 25-hydroxylase. The inhibition of vitamin D3 25-hydroxylating system in hepatocytes contributed to a significant reduction in blood serum 25OHD3.
The ROS-generating and antioxidant systems in the liver of rats treated with prednisolone and vitamin D(3)
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;
e-mail: ishymansk@inbox.ru
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.