Protective effects of vitamin D on ischemia-reperfusion injury of the ovary in a rat model

Document Type : Original Article


1 Department of Obstetrics and Gynecology, Giresun University, Giresun, Turkey

2 Department of Cardiovascular Surgery, Giresun University, Giresun, Turkey

3 Department of Pathology, Kafkas University, Kars, Turkey

4 Department of Pharmacology, Giresun University, Giresun, Turkey


Objective(s): The aim of the present study is to investigate probable acute effects of vitamin D on ischemia-reperfusion injury in the rat ovary.
Materials and Methods: A group of 30 Wistar albino rats was divided into five groups of 6 each. Group 1:  underwent laparotomy only and the ovaries were removed. Group 2:  3-hr ischemia followed by excision of the ovaries. Group 3:  3-hr ischemia and 3-hr reperfusion and the ovaries were removed. Group 4:  vitamin D was administered 30 min prior to the 3-hr of ischemia and the ovaries were excised at the end of ischemia period. Group 5:  vitamin D was administered 30 min prior to the 3-hr of ischemia and 3-hr reperfusion then the ovaries were removed at the end of reperfusion. The ovaries excised in each group also underwent biochemical and histopathologic analysis. MDA (malondialdehyde), SOD (superoxide dismutase), NO (nitric oxide), TAS (total antioxidant score), TOS (total oxidant score) were analyzed as biochemical parameters.
Results: There were no significant differences between groups in TAS, TOS, or OSI (P>0.05). MDA levels were lower in the vitamin D treatment groups especially in group 5, significantly (P<0.05). In the histopathologic evaluation, we established that an improvement with vitamin D treatment. According to tissue injury scores, vascular congestion score was significantly different between group 3 and 5 (P<0.05).
Conclusion: Vitamin D seems an effective molecule for protection of ischemia-reperfusion injury in rat ovary. There is some significant improvement in oxidative damages with vitamin D treatment.


Main Subjects

1. Hibbard L. Adnexal torsion. Am J Obstet Gynecol 1985;152 :456–461.
2. Becker JH, de Graaff J, Vos MC. Torsion of the ovary: a known but frequently missed diagnosis. Eur J Emerg Med 2009;16 :124-126.
3. Chen M, Chen CD, Yang YS. Torsion of the previously normal uterine adnexa. Evaluation of the correlation between the pathological changes and the clinical characteristics. Acta Obstet Gynecol Scand 2001;80:58-61.
4. Huchon C, Fauconnier A. Adnexal torsion: a literature review. Eur J Obstet Gynecol Reprod Biol 2010;150: 8-12.
5. McCord JM. Oxygen-derived free radicals in postischemic tissue injury. N Engl J Med 1985;312:159-163.
6. Zimmerman BJ, Granger DN. Reperfusion injury. Surg Clin North Am. 1992;72: 65-83.
7. Sozer S, Diniz G, Lermioglu F. Effects of celecoxib in young rats: histopathological changes in tissues and alterations of oxidative stress/antioxidant defense system. Arch Pharm Res 2011;34: 253-259.
8. Tok A, Sener E, Albayrak A, Cetin N, Polat B, Suleyman B, et al. Effect of mirtazapine on oxidative stress created in rat kidneys by ischemia-reperfusion. Ren Fail 2012;34: 103-110.
9. Akdemir A, Erbas O, Ergenoglu M, Ozgur Yeniel A, Oltulu F, Yavasoglu A, et al. Montelukast prevents ischaemia/reperfusion-induced ovarian damage in rats. Eur J Obstet Gynecol Reprod Biol 2014;173: 71-76.
10. Abali R, Tasdemir N, Yuksel MA, Guzel S, Oznur M, Nalbantoglu B, et al. Protective effect of infliximab on ischemia/reperfusion injury in a rat ovary model: biochemical and histopathologic evaluation. Eur J Obstet Gynecol Reprod Biol 2013;171: 353-357.
11. Yurtcu E, Togrul C, Ozyer S, Uzunlar O, Karatas YH, Seckin KD, et al. Dose dependent protective effects of vardenafil on ischemia-reperfusion injury with biochemical and histopathologic evaluation in rat ovary. J Pediatr Surg 2015; 50:1205-1209.
12. Sapmaz-Metin M, Topcu-Tarladacalisir Y, Uz YH, Inan M, Omurlu IK, Cerkezkayabekir A, et al. Vitamin E modulates apoptosis and c-jun N-terminal kinase activation in ovarian torsion-detorsion injury. Exp Mol Pathol 2013; 95:213-219.
13. Walentowicz-Sadlecka M, Sadlecki P, Walentowicz P, Grabiec M. [The role of vitamin D in the carcinogenesis of breast and ovarian cancer]. Ginekol Pol 2013; 84: 305-308.
14. Bae S, Singh SS, Yu H, Lee JY, Cho BR, Kang PM. Vitamin D signaling pathway plays an important role in the development of heart failure after myocardial infarction. J Appl Physiol 2013;114:979-987.
15. Stratos I, Li Z, Herlyn P, Rotter R, Behrendt AK, Mittlmeier T, et al. Vitamin D increases cellular turnover and functionally restores the skeletal muscle after crush injury in rats. Am J Pathol 2013;182: 895-904.
16. Assalin HB, Rafacho BP, dos Santos PP, Ardisson LP, Roscani MG, Chiuso-Minicucci F, et al. Impact of the length of vitamin D deficiency on cardiac remodeling. Circ Heart Fail 2013;6: 809-816.
17. Sinanoglu O, Sezgin G, Ozturk G, Tuncdemir M, Guney S, Aksungar FB, et al. Melatonin with 1,25-dihydroxyvitamin D3 protects against apoptotic ischemia-reperfusion injury in the rat kidney. Ren Fail. 2012; 34:1021-1026.
18. Seif AA, Abdelwahed DM. Vitamin D ameliorates hepatic ischemic/reperfusion injury in rats. J Physiol Biochem 2014; 70:659-666.
19. Erel O. A new automated colorimetric method for measuring total oxidant status. Clin Biochem. 2005;38:1103-1111.
20. Harma M, Harma M, Erel O. Increased oxidative stress in patients with hydatidiform mole. Swiss Med Wkly 2003; 133 :563-566.
21. Guven S, Muci E, Unsal MA, Yulug E, Alver A, Kadioglu Duman M, et al. The effects of carbon dioxide pneumoperitoneum on ovarian blood flow, oxidative stress markers, and morphology during laparoscopy: a rabbit model. Fertil Steril 2010;93 1327-1332.
22. Lin E, Lowry S, Calvano S. The systemic response to injury. Principles of Surgery. 7th ed. New York: McGraw-Hill; 1999.
23. White BC, Grossman LI, Krause GS. Brain injury by global ischemia and reperfusion: a theoretical perspective on membrane damage and repair. Neurology 1993;43:1656-1665.
24. Erkanli Senturk G, Erkanli K, Aydin U, Yucel D, Isiksacan N, Ercan F, et al. The protective effect of oxytocin on ischemia/reperfusion injury in rat urinary bladder. Peptides 2013; 40: 82-88.
25. Lee DM, Hoffman WH, Carl GF, Khichi M, Cornwell PE. Lipid peroxidation and antioxidant vitamins prior to, during, and after correction of diabetic ketoacidosis. J Diabetes Complications 2002; 16:294-300.
26. Yigiter M, Halici Z, Odabasoglu F, Keles ON, Atalay F, Unal B, et al. Growth hormone reduces tissue damage in rat ovaries subjected to torsion and detorsion: biochemical and histopathologic evaluation. Eur J Obstet Gynecol Reprod Biol 2011; 157: 94-100.
27. Bakan V, Ciralik H, Tolun FI, Atli Y, Mil A, Ozturk S. Protective effect of erythropoietin on torsion/detorsion injury in rat model. J Pediatr Surg 2009; 44:1988-1994.
28. Ferdinandy P. Peroxynitrite: just an oxidative/nitrosative stressor or a physiological regulator as well? Br J Pharmacol 2006;148: 1-3.
29. Gungor AN, Turkon H, Albayrak A, Ovali M, Islimye M, Gencer M, et al. Does Omegaven have beneficial effects on a rat model of ovarian ischemia/reperfusion? Eur J Obstet Gynecol Reprod Biol 2014; 181: 240-245.
30. Demiryilmaz I, Sener E, Cetin N, Altuner D, Akcay F, Suleyman H. A comparative investigation of biochemical and histopathological effects of thiamine and thiamine pyrophosphate on ischemia-reperfusion induced oxidative damage in rat ovarian tissue. Arch Pharm Res 2013; 36:1133-1139.
31. Tan X, Wen X, Liu Y. Paricalcitol inhibits renal inflammation by promoting vitamin D receptor-mediated sequestration of NF-kappaB signaling. J Am Soc Nephrol 2008;19:1741-1752.
32. Azak A, Huddam B, Haberal N, Kocak G, Ortabozkoyun L, Senes M, et al. Effect of novel vitamin D receptor activator paricalcitol on renal ischaemia/reperfusion injury in rats. Ann R Coll Surg Engl 2013; 95: 489-494.
33. Caglayan EK, Caglayan K, Gocmen AY, Cinar H, Seckin L, Seckin S, et al. Protective effect of ethyl pyruvate on ischemia-reperfusion injury in rat ovary: biochemical and histopathological evaluation. Eur J Obstet Gynecol Reprod Biol 2014; 182: 154-159.
34. Akdemir A, Erbas O, Gode F, Ergenoglu M, Yeniel O, Oltulu F, et al. Protective effect of oxytocin on ovarian ischemia-reperfusion injury in rats. Peptides 2014; 55: 126-130.
35. Bozkurt S, Arikan DC, Kurutas EB, Sayar H, Okumus M, Coskun A, et al. Selenium has a protective effect on ischemia/reperfusion injury in a rat ovary model: biochemical and histopathologic evaluation. J Pediatr Surg 2012; 47:1735-1741.
36. Ergun Y, Koc A, Dolapcioglu K, Akaydin Y, Dogruer G, Kontas T, et al. The protective effect of erythropoietin and dimethylsulfoxide on ischemia-reperfusion injury in rat ovary. Eur J Obstet Gynecol Reprod Biol 2010;152: 186-190.
37. Sayyah-Melli M, Rashidi MR, Kaseb-Ganeh M, Rashtchizadeh N, Taghavi S, Ouladsahebmadarek E, et al. The effect of erythropoietin against oxidative damage associated with reperfusion following ovarian detorsion. Eur J Obstet Gynecol Reprod Biol 2012;162:182-186.
38. Sengul O, Ferah I, Polat B, Halici Z, Bayir Y, Yilmaz M, et al. Blockade of endothelin receptors with bosentan limits ischaemia/reperfusion-induced injury in rat ovaries. Eur J Obstet Gynecol Reprod Biol 2013;170:458-463.
39. Liou KT, Shen YC, Chen CF, Tsao CM, Tsai SK. Honokiol protects rat brain from focal cerebral ischemia-reperfusion injury by inhibiting neutrophil infiltration and reactive oxygen species production. Brain Res 2003;992:159-166.
40. Cakir Gungor AN, Gencer M, Karaca T, Hacivelioglu S, Uysal A, Korkmaz F, et al. The effect of hesperetin on ischemia-reperfusion injury in rat ovary. Arch Gynecol Obstet 2014; 290: 763-769.