Said Said ELSHAMA, Hosam-Eldin Hussein OSMAN, Ayman El-Meghawry EL-KENAWY, Mohamed YOUSEEF

Comparison between the protective effects of vitamin K and vitamin A on the modulation of hypervitaminosis D3 short-term toxicity in adult albino rats

Background/aim: Vitamin D3has increased risk of toxicity due to its common use in multivitamin preparations. Vitamin K and vitamin A play an important role in vitamin D action. The goal of the current study was to compare the protective effects of vitamin K and vitamin A on the modulation of hypervitaminosis D3toxicity in rats by assessing serum calcium, renal function tests, cardiac enzymes, and related histopathological changes. Materials and methods: Eighty adult albino rats were divided into four groups; each group consisted of 20 rats. The first group received water; the second received a toxic dose of vitamin D3 ; the third received a toxic dose of vitamin D3with vitamin A; and the fourth received a toxic dose of vitamin D3with vitamin K. Results: Vitamin D3toxicity led to significant abnormalities of cardiac enzymes, renal function tests, and serum calcium associated with histopathological changes in the kidney, heart, lung, adrenal gland, and aorta. Individual administration of vitamin A or vitamin K with a toxic dose of vitamin D improved the biochemical and histopathological abnormalities of hypervitaminosis D3 . Conclusion: Vitamins A and K showed the same protective effects in the modulation of hypervitaminosis D3 short-term toxicity.

PDF

___

1. McDonald A, Smith SM. The Complete Book of Vitamins and Minerals. Lincolnwood, IL, USA: Publications International; 1996.
2. Sandhu HS. Textbook of Veterinary Toxicology. 2nd ed. New Delhi, India: Kalyani Publishers; 2009.
3. Weaver CM, Fleet JC. Vitamin D requirements: current and future. Am J Clin Nutr 2004; 80 (Suppl): 1735S1739S.
4. Holick MF. Vitamin D: its role in cancer prevention and treatment. Prog Biophys Mol Biol 2006; 92: 4959.
5. Chavhan SG, Brar RS, Banga HS, Sandhu HS, Sodhi S, Gadhave PD, Kothule VR, Kammon AM. Clinicopathological studies on vitamin D3 toxicity and therapeutic evaluation of Aloe vera in rats. Toxicol Int 2011; 18: 3543.
6. Craciun AM, Wolf J, Knapen MH, Brouns F, Vermeer C. Improved bone metabolism in female elite athletes after vitamin K supplementation. Int J Sports Med 1998; 19: 479 484.
7. Sanchez-Martinez R, Castillo A, Steinmeyer A, Aranda A. The retinoid X receptor ligand restores defective signalling by the vitamin D receptor. EMBO Rep 2006; 7: 10301034.
8. da Rocha RF, de Oliveira MR, Schonhofen P, Schnorr CE, Dal Pizzol F, Moreira JC. Long-term vitamin A supplementation at therapeutic doses induces mitochondrial electrons transfer chain (METC) impairment and increased mitochondrial membrane-enriched fraction (MMEF) 3-nitrotyrosine on rat heart. Free Radic Res 2010; 44: 505512.
9. Alarcón-Corredor OM, Alfonso R. Clinical and biochemical alterations in rats treated with high doses of vitamin A. Arch Latinoam Nutr 2007; 57: 224230 (article in Spanish with an abstract in English).
10. De Jonghe S, Verbeeck J, Vinken P, Lammens L, Starckx S, Lachau-Durand S, Bouche MP, Willems B, Coussement W. Hemorrhagic cardiomyopathy in male mice treated with an NNRTI: the role of vitamin K. Toxicol Pathol 2008; 36: 321 329.
11. Alexander RH, Griffith JM. Clinical/Nutritional Biochemistry. Basic Biochemical Methods. 2nd ed. New York, NY, USA: John Wiley & Sons; 1992.
12. Janssen JW, Helbing AR. Arsenazo III: an improvement of the routine calcium determination in serum. Eur J Clin Chem Clin Biochem 1991; 29: 197201.
13. Wu AH, Apple FS, Gibler, WB, Jesse RL, Warshaw MM, Valdes R Jr. National Academy of Clinical Biochemistry Standards of Laboratory Practice: recommendations for use of cardiac markers in coronary artery diseases. Clin Chem 1999; 45: 11041121.
14. Bancroft JD, Gamble M. Theory and Practice Histological Techniques. 5th ed. New York, NY, USA: Churchill Livingstone; 2002.
15. Döneray H, Özkan B, Özkan A, Koşan C, Orbak Z, Karakelleoğlu C. The clinical and laboratory characteristic of vitamin D intoxication in children. Turk J Med Sci 2009; 39: 14.
16. Patel S, Farragher T, Berry J, Bunn D, Silman A, Symmons D. Association between serum vitamin D metabolite levels and disease activity in patients with early inflammatory polyarthritis. Arthritis Rheum 2007; 56: 21432149.
17. Freedman DM, Looker AC, Chang SC, Graubard BI. Prospective study of serum vitamin D and cancer mortality in the United States. J Natl Cancer Inst 2007; 99: 15941602.
18. Özkan B, Hatun Ş, Bereket A. Vitamin D intoxication. The Turkish Journal of Pediatrics 2012; 54: 9398.
19. Ralston SH, Coleman R, Fraser WD, Gallagher SJ, Hosking DJ, Iqbal JS, McCloskey E, Sampson, D. Medical management of hypercalcemia. Calcif Tissue Int 2004; 74: 111.
20. Jones G. Pharmacokinetics of vitamin D toxicity. Am J Clin Nutr 2008; 88: 582S586S.
21. Koul PA, Ahmad SH, Ahmad F, Jan RA, Shah SU, Khan UH. Vitamin D toxicity in adults: a case series from an area with endemic hypovitaminosis D. Oman Med J 2011; 26: 201204.
22. Kerr DN. Hypercalcemia and metastatic calcification. Cardiovasc Res 1997; 36: 293297.
23. Drüeke TB, Massy ZA. Role of vitamin D in vascular calcification: bad guy or good guy? Nephrol Dial Transplant 2012; 27: 17041707.
24. Kingma JG Jr, Roy PE. Effect of ethane-1-hydroxy1,1-diphosphonate on arterial calcinosis induced by hypervitaminosis D: a morphologic investigation. J Exp Pathol (Oxford) 1990; 71: 145153.
25. Walentynowicz O, Kubasik-Juraniec J, Rudzińska-Kisil T. Myocardial necrosis due to vitamin D3 overdose--scanning electron microscopic observations. Folia Morphol (Warsz) 2004; 63: 439444.
26. Jeremias A, Gibson CM. Narrative review: alternative causes for elevated cardiac troponin levels when acute coronary syndromes are excluded. Ann Intern Med 2005; 142: 786791.
27. OBrien PJ. Cardiac troponin is the most effective translational safety biomarker for myocardial injury in cardiotoxicity. Toxicology 2008; 245: 206218.
28. Adams J, Pepping J. Vitamin K in the treatment and prevention of osteoporosis and arterial calcification. Am J Health Syst Pharm 2005; 62: 15741581.
29. Fu X, Moreines J, Booth SL. Vitamin K supplementation does not prevent bone in ovariectomized Norway rats. Nutr Metab 2012; 9: 12.
30. Ferland G. The vitamin K-dependent proteins: an update. Nutr Rev 1998; 56: 223230.
31. El-Morsy AS, Beshir SR, Farrag KA, Mohamed MS, Hamam GG. Comparative study on the effect of vitamin K versus combined Ca and vitamin D administration on the prevention of experimentally-induced osteoporosis in adult male albino rats. The Egyptian Journal of Histology 2011; 34: 514.
32. Beers MH, Berkow R, editors. The Merck Manual of Diagnosis and Therapy. 17th ed. Rahway, NJ, USA: Merck and Company; 2004.
33. Penniston KL, Tanumihardjo SA. The acute and chronic toxic effects of vitamin A. Am J Clin Nutr 2006; 83: 191201.
34. Johansson S, Melhus H. Vitamin A antagonizes calcium response to vitamin D in man. J Bone Miner Res 2001; 16: 18991905.
35. Sommer A. Uses and misuses of vitamin A. Curr Issues Public Health 1996; 2: 161164.
36. Rohde CM, DeLuca H. Bone resorption activity of all-trans retinoic acid is independent of vitamin D in rats. J Nutr 2003; 133: 777783.
37. Rohde CM, Manatt M, Clagett-Dame M, DeLuca HF. Vitamin A antagonizes the action of vitamin D in rats. J Nutr 1999; 129: 22462250.
38. Masterjohn C. Vitamin D toxicity redefined: vitamin K and the molecular mechanism. Med Hypotheses 2007; 68: 10261034.
39. Price PA, Buckley JR, Williamson MK. The amino bisphosphonate ibandronate prevents vitamin D toxicity and inhibits vitamin D-induced calcification of arteries, cartilage, lungs and kidneys in rats. J Nutr 2001; 131: 29102915.