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.