Ukr.Biochem.J. 2016; Volume 88, Issue 5, Sep-Oct, pp. 38-47

doi: https://doi.org/10.15407/ubj88.05.038

Prednisolone and vitamin D(3) modulate oxidative metabolism and cell death pathways in blood and bone marrow mononuclear cells

07.11.2016   Uncategorized   No comments

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.

Keywords: , , , , , , ,

References:

  1. Hartmann K, Koenen M, Schauer S, Wittig-Blaich S, Ahmad M, Baschant U, Tuckermann JP. Molecular Actions of Glucocorticoids in Cartilage and Bone During Health, Disease, and Steroid Therapy. Physiol Rev. 2016 Apr;96(2):409-47. Review. PubMed, CrossRef
  2. Buehring B, Viswanathan R, Binkley N, Busse W. Glucocorticoid-induced osteoporosis: an update on effects and management. J Allergy Clin Immunol. 2013 Nov;132(5):1019-30. Review. PubMed, CrossRef
  3. Lin H, Gao X, Chen G, Sun J, Chu J, Jing K, Li P, Zeng R, Wei B. Indole-3-carbinol as inhibitors of glucocorticoid-induced apoptosis in osteoblastic cells through blocking ROS-mediated Nrf2 pathway. Biochem Biophys Res Commun. 2015 May 1;460(2):422-7. PubMed, CrossRef
  4. Shymanskyy IO, Khomenko AV, Lisakovska OO, Labudzynskyi DO, Apukhovska LI, Veliky MM. The ROS-generating and antioxidant systems in the liver of rats treated with prednisolone and vitamin D3. Ukr Biochem J. 2014 Sep-Oct;86(5):111-25. (In Ukrainian). PubMed, CrossRef
  5. Saccone D, Asani F, Bornman L. Regulation of the vitamin D receptor gene by environment, genetics and epigenetics. Gene. 2015 May 1;561(2):171-80. Review. PubMed, CrossRef
  6. Basit S. Vitamin D in health and disease: a literature review. Br J Biomed Sci. 2013;70(4):161-72. PubMed, CrossRef
  7. Jain SK, Micinski D. Vitamin D upregulates glutamate cysteine ligase and glutathione reductase, and GSH formation, and decreases ROS and MCP-1 and IL-8 secretion in high-glucose exposed U937 monocytes. Biochem Biophys Res Commun. 2013 Jul 19;437(1):7-11. PubMed, PubMedCentral, CrossRef
  8. Cheng Q, Barboule N, Frit P, Gomez D, Bombarde O, Couderc B, Ren GS, Salles B, Calsou P. Ku counteracts mobilization of PARP1 and MRN in chromatin damaged with DNA double-strand breaks. Nucleic Acids Res. 2011 Dec;39(22):9605-19. PubMed, PubMedCentral, CrossRef
  9. Khomenko AV. Cholecalciferol hydroxylation in rat hepatocytes under the influence of prednisolone. Ukr Biokhim Zhurn. 2013 May-Jun;85(3):90-5. (In Ukrainian). PubMed, CrossRef
  10. Keeney JT, Förster S, Sultana R, Brewer LD, Latimer CS, Cai J, Klein JB, Porter NM, Butterfield DA. Dietary vitamin D deficiency in rats from middle to old age leads to elevated tyrosine nitration and proteomics changes in levels of key proteins in brain: implications for low vitamin D-dependent age-related cognitive decline. Free Radic Biol Med. 2013 Dec;65:324-34. PubMed, PubMedCentral, CrossRef
  11. Forman HJ, Augusto O, Brigelius-Flohe R, Dennery PA, Kalyanaraman B, Ischiropoulos H, Mann GE, Radi R, Roberts LJ 2nd, Vina J, Davies KJ. Even free radicals should follow some rules: a guide to free radical research terminology and methodology. Free Radic Biol Med. 2015 Jan;78:233-5. PubMed, CrossRef
  12. Shymanskyy IO, Lisakovska OO, Mazanova AO, Riasniy VM, Veliky MM. Effects of vitamin D3 and vitamin E on prednisolone-induced alterations of phagocyte function. Eur Rev Med Pharmacol Sci. 2016 Apr;20(7):1379-83. PubMed
  13. Shi J, Wang L, Zhang H, Jie Q, Li X, Shi Q, Huang Q, Gao B, Han Y, Guo K, Liu J, Yang L, Luo Z. Glucocorticoids: Dose-related effects on osteoclast formation and function via reactive oxygen species and autophagy. Bone. 2015 Oct;79:222-32.  PubMed, CrossRef
  14. Omori Y, Mano T, Ohtani T, Sakata Y, Takeda Y, Tamaki S, Tsukamoto Y, Miwa T, Yamamoto K, Komuro I. Glucocorticoids Induce Cardiac Fibrosis via Mineralocorticoid Receptor in Oxidative Stress: Contribution of Elongation Factor Eleven-Nineteen Lysine-Rich Leukemia (ELL). Yonago Acta Med. 2014 Sep;57(3):109-16. PubMed, PubMedCentral
  15. Olteanu D, Filip A, Mureşan A, Nagy A, Tabaran F, Moldovan R, Decea N, Catoi C, Clichici S. The effects of chitosan and low dose dexamethasone on extrahepatic cholestasis after bile duct ligation in Wistar rats. Acta Physiol Hung. 2012 Mar;99(1):61-73. PubMed, CrossRef
  16. Stahn C, Buttgereit F. Genomic and nongenomic effects of glucocorticoids. Nat Clin Pract Rheumatol. 2008 Oct;4(10):525-33. Review. PubMed, CrossRef
  17. Rizvi A, Farhan M, Naseem I, Hadi SM. Calcitriol-copper interaction leads to non enzymatic, reactive oxygen species mediated DNA breakage and modulation of cellular redox scavengers in hepatocellular carcinoma. Apoptosis. 2016 Sep;21(9):997-1007. PubMed, CrossRef
  18. Benvenuti S, Brandi ML. Corticosteroid-induced osteoporosis: pathogenesis and prevention. Clin Exp Rheumatol. 2000 Jul-Aug;18(4 Suppl 20):S64-6. Review. PubMed
  19. Kim HJ. New understanding of glucocorticoid action in bone cells. BMB Rep. 2010 Aug;43(8):524-9. PubMed, CrossRef
  20. Pennisi P, D’Alcamo MA, Leonetti C, Clementi A, Cutuli VM, Riccobene S, Parisi N, Fiore CE. Supplementation of L-arginine prevents glucocorticoid-induced reduction of bone growth and bone turnover abnormalities in a growing rat model. J Bone Miner Metab. 2005;23(2):134-9. PubMed, CrossRef
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