Potential therapeutic effect of pomegranate seed oil on ovarian ischemia/reperfusion injury in rats

Document Type: Original Article


1 Department of Pharmacology, Faculty of Medicine, Kafkas University, Kars, Turkey

2 Department of Pathology, Highlited sentences should be cahanged as Canakkale Onsekiz Mart University Faculty of Medicine, 17100 Canakkale/Turkey

3 Department of Biology, Canakkale Onsekiz Mart University Faculty of Medicine, 17100 Canakkale/Turkey

4 Department of Histology and Embryology, Ataturk University, Faculty of Medicine, 25240 Erzurum/Turkey


Objective(s): The aim of this study is to determine the therapeutic effects of pomegranate seed oil, which is a powerful antioxidant and anti-inflammatory agent, on ovarian-ischemia and reperfusion injury in rats.
Materials and Methods: Fifty-six  female albino Wistar rats were divided into 7 equal groups. Group 1; Sham Operation, Group 2; Ischemia, Group 3; Ischemia + Reperfusion, Group 4; Ischemia + Pomegranate 0,32 ml / kg (IP), Group 5; Ischemia + Pomegranate 0.64 ml / kg, Group 6; Ischemia + Pomegranate 0,32 ml / kg + reperfusion, Group 7; Ischemia + Pomegranate 0,64 ml / kg + reperfusion. Three hours after ischemia and 3 hours after reperfusion, the study was terminated.
Results: While NADPH oxidase activity, MDA and TNF-α levels were significantly increased, SOD activity and GSH levels were reduced in ischemia and I/R groups. Low dose pomegranate seed oil  application reduced significantly oxidative stress and NADPH oxidase activity in both ischemic and ischemic/reperfusion groups. At the same time, low-dose pomegranate seed oil extract reduced TNF-α levels and significantly increased antioxidant activity.
Conclusion: PSO demonstrated an important therapeutic effect in the treatment of ovarian ischemia and reperfusion injury.


Main Subjects

1. Hibbard LT. Adnexal torsion. Am J Obstet Gynecol 1985; 152:456-461.
2. Hasiakos D, Papakonstantinou K, Kontoravdis A, Gogas L, Aravantinos L, Vitoratos N. Adnexal torsion during pregnancy: report of four cases and review of the literature. J Obstet Gynaecol Res 2008; 34:683-687.
3. Kalogeris T, Baines CP, Krenz M, Korthuis RJ. Cell biology of ischemia/reperfusion injury. Int Rev Cell Mol Biol 2012; 298:229-317.
4. Kroemer G, Galluzzi L, Brenner C. Mitochondrial membrane permeabilization in cell death. Physiol Rev 2007; 87:99-163.
5. Broughton BR, Reutens DC, Sobey CG. Apoptotic mechanisms after cerebral ischemia. Stroke 2009; 40:e331-339.
6. Cerqueira NF, Hussni CA, Yoshida WB. Pathophysiology of mesenteric ischemia/reperfusion: a review. Acta Cir Bras 2005; 20:336-343.
7. Piper HM, Meuter K, Schafer C. Cellular mechanisms of ischemia-reperfusion injury. Ann Thorac Surg 2003; 75:S644-648.
8. Perrelli MG, Pagliaro P, Penna C. Ischemia/reperfusion injury and cardioprotective mechanisms: Role of mitochondria and reactive oxygen species. World J Cardiol 2011; 3:186-200.
9. Bedriniam Yilmaz, Usta. C. Therapauetic effects of punica granatum. Türk Aile Hek Derg 2010; 14:146-153.
10. Lansky EP, Newman RA. Punica granatum (pomegranate) and its potential for prevention and treatment of inflammation and cancer. J Ethnopharmacol 2007; 109:177-206.
11. Afaq F, Saleem M, Krueger CG, Reed JD, Mukhtar H. Anthocyanin- and hydrolyzable tannin-rich pomegranate fruit extract modulates MAPK and NF-kappaB pathways and inhibits skin tumorigenesis in CD-1 mice. Int J Cancer 2005; 113:423-433.
12. Gil MI, Tomas-Barberan FA, Hess-Pierce B, Holcroft DM, Kader AA. Antioxidant activity of pomegranate juice and its relationship with phenolic composition and processing. J Agric Food Chem 2000; 48:4581-4589.
13. Xu J, Guo CJ, Yang JJ, Wei JY, Li YF, Pang W, et al. [Intervention of antioxidant system function of aged rats by giving fruit juices with different antioxidant capacities]. Zhonghua Yu Fang Yi Xue Za Zhi 2005; 39:80-83.
14. Aviram M, Rosenblat M. Pomegranate Protection against Cardiovascular Diseases. Evid Based Complement Alternat Med 2012; 2012:382763.
15. Viladomiu M, Hontecillas R, Lu P, Bassaganya-Riera J. Preventive and prophylactic mechanisms of action of pomegranate bioactive constituents. Evid Based Complement Alternat Med 2013; 2013:789764.
16. Aksak Karamese S, Toktay E, Unal D, Selli J, Karamese M, Malkoc I. The protective effects of beta-carotene against ischemia/reperfusion injury in rat ovarian tissue. Acta Histochem 2015; 117:790-797.
17. Bayir Y, Cadirci E, Polat B, Kilic Baygutalp N, Albayrak A, Karakus E, et al. Aliskiren - a promising strategy for ovarian ischemia/reperfusion injury protection in rats via RAAS. Gynecol Endocrinol 2016; 32:675-683.
18. Tatar A, Yayla M, Kose D, Halici Z, Yoruk O, Polat E. The role of endothelin-1 and endothelin receptor antagonists in allergic rhinitis inflammation: ovalbumin-induced rat model. Rhinology 2016; 54:266-272.
19. Palabiyik SS, Karakus E, Akpinar E, Halici Z, Bayir Y, Yayla M, et al. The role of urotensin receptors in the paracetamol-induced hepatotoxicity model in mice: ameliorative potential of urotensin II antagonist. Basic Clin Pharmacol Toxicol 2016; 118:150-159.
20. Hashem HE, Abd El-Haleem MR, Amer MG, Bor’i A. Pomegranate protective effect on experimental ischemia/reperfusion retinal injury in rats (histological and biochemical study). Ultrastruct Pathol 2017; 41:346-357.
21. Ahmed MA, El Morsy EM, Ahmed AA. Pomegranate extract protects against cerebral ischemia/reperfusion injury and preserves brain DNA integrity in rats. Life Sci 2014; 110:61-69.
22. Sancaktutar AA, Bodakci MN, Hatipoglu NK, Soylemez H, Basarili K, Turkcu G. The protective effects of pomegranate extracts against renal ischemia-reperfusion injury in male rats. Urol Ann 2014; 6:46-50.
23. Boroushaki MT, Asadpour E, Sadeghnia HR, Dolati K. Effect of pomegranate seed oil against gentamicin -induced nephrotoxicity in rat. J Food Sci Technol 2014; 51:3510-3514.
24. Dorweiler B, Pruefer D, Andrasi TB, Maksan SM, Schmiedt W, Neufang A, et al. Ischemia-Reperfusion Injury : Pathophysiology and Clinical Implications. Eur J Trauma Emerg Surg 2007; 33:600-612.
25. Collard CD, Gelman S. Pathophysiology, clinical manifestations, and prevention of ischemia-reperfusion injury. Anesthesiology 2001; 94:1133-1138.
26. Bedard K, Krause KH. The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev 2007; 87:245-313.
27. Maru Y, Nishino T, Kakinuma K. Expression of Nox genes in rat organs, mouse oocytes, and sea urchin eggs. DNA Seq 2005; 16:83-88.
28. Kim YS, Morgan MJ, Choksi S, Liu ZG. TNF-induced activation of the Nox1 NADPH oxidase and its role in the induction of necrotic cell death. Mol Cell 2007; 26:675-687.
29. Kahles T, Kohnen A, Heumueller S, Rappert A, Bechmann I, Liebner S, et al. NADPH oxidase Nox1 contributes to ischemic injury in experimental stroke in mice. Neurobiol Dis 2010; 40:185-192.
30. Ferreira LM, Sari MHM, Cervi VF, Gehrcke M, Barbieri AV, Zborowski VA, et al. Pomegranate seed oil nanoemulsions improve the photostability and in vivo antinociceptive effect of a non-steroidal anti-inflammatory drug. Colloids Surf B Biointerfaces 2016; 144:214-221.
31. Costantini S, Rusolo F, De Vito V, Moccia S, Picariello G, Capone F, et al. Potential anti-inflammatory effects of the hydrophilic fraction of pomegranate (Punica granatum L.) seed oil on breast cancer cell lines. Molecules 2014; 19:8644-8660.
32. Boussetta T, Raad H, Letteron P, Gougerot-Pocidalo MA, Marie JC, Driss F, et al. Punicic acid a conjugated linolenic acid inhibits TNFalpha-induced neutrophil hyperactivation and protects from experimental colon inflammation in rats. PLoS One 2009; 4:e6458.
33. Polat B, Albayrak A, Halici Z, Karakus E, Bayir Y, Demirci E, et al. The effect of levosimendan in rat mesenteric ischemia/reperfusion injury. J Invest Surg 2013; 26:325-333.
34. Albayrak Y, Halici Z, Odabasoglu F, Unal D, Keles ON, Malkoc I, et al. The effects of testosterone on intestinal ischemia/reperfusion in rats. J Invest Surg 2011; 24:283-291.
35. Vehbi Yavuz Tokgoz, Mehmet Sipahi, Ozlem Keskin, Gulname Findik Guvendi, Takir S. Protective effects of vitamin D on ischemia-reperfusion injury of the ovary in a rat model. Iran J Basic Med Sci 2017; 21:593-599.
36. West T, Atzeva M, Holtzman DM. Pomegranate polyphenols and resveratrol protect the neonatal brain against hypoxic-ischemic injury. Dev Neurosci 2007; 29:363-372.
37. Shaban NZ, El-Kersh MA, El-Rashidy FH, Habashy N. Protective role of Punica granatum (pomegranate) peel and seed oil extracts on diethylnitrosamine and phenobarbital-induced hepatic injury in male rats. Food Chem 2013; 141:1587-1596.