The Impact of Chrysin on The Folliculogenesis and Ovarian Apoptosis in Ischemia-Reperfusion Injury in The Rat Model

Document Type : Original Article


1 Student Research Committee, Gonabad University of Medical Sciences, Gonabad, Iran.

2 Student Research Committee, Gonabad University of Medical Sciences, Gonabad, Iran

3 Deartment of Obstetrics and Gynecology, Gonabad University of Medical Sciences, Gonabad, Iran

4 Deartment of Anatomy, School of Medicine, Gonabad University of Medical Sciences, Gonabad, Iran

5 Clnical Research Development Unit of Tabriz Valiasr Hospital, Tabriz University of Medical Sciences, Tabriz, Iran

6 Deartment of Biochemistry, School of Medicine, Gonabad University of Medical Sciences, Gonabad, Iran

7 Deartment of Physiology, School of Medicine, Gonabad University of Medical Sciences, Gonabad, Iran

8 Nusing Research Center, Gonabad University of Medical Sciences, Gonabad, Iran


Background: The ovarian Ischemia/reperfusion is one of the gynecological emergency concerns that may lead to the ovary damage and folliculogenesis. The present research aimed to evaluate the impact of the Chrysin (CH) on the ischemia-reperfusion (I/R) injury in the rat model.
Materials and Methods: In this experimental research, 48 adult female rats, 8 weeks age and 180-200 g weight, have been categorized into 6 equal groups (n=8) including one sham and 5 ovarian torsion groups (OT+CH groups) that received different treatments. Each group has been treated 30 min before detorsion with gavage of CH or normal saline for 1 week and pregnant mare serum gonadotropin (PMSG) has been injected on the day 5 for initiating folliculogenesis. Finally, bio-chemical, molecular, histopathological, apoptotic and hormonal evaluations were performed.
Results: The anti-oxidant enzyme, superoxide dismutase and glutathione peroxidase, ameliorated in the ovarian tissues of the OT+CH groups in comparison with the OT group (P


1. Elmimehr R, Motamed-Sanaye A, Brazvan B, Abtahi-Eivary SH, Moghimian M, Fani M. Effects of hypothermia and pentoxifylline on the adnexal torsion/detorsion injuries in a rat testis model. Andrologia. 2021; 53(8): e14143.                      2. McWilliams GD, Hill MJ, Dietrich III CS. Gynecologic emergencies. Surg Clin North Am. 2008; 88(2): 265-283.
3. Somuncu S, Cakmak M, Dikmen G, Akman H, Kaya M. Ischemia-reperfusion injury of rabbit ovary and protective effect of trapidil: an experimental study. Pediatr Surg Int. 2008; 24(3): 315-318.
4. Sasaki KJ, Miller CE. Adnexal torsion: review of the literature. J Minim Invasive Gynecol. 2014; 21(2): 196-202.
5. Khaje Roshanaee M, Abtahi-Eivary SH, Shokoohi M, Fani M, Mahmoudian A, Moghimian M. Protective effect of minocycline on Bax and Bcl-2 gene expression, histological damages and oxidative stress induced by ovarian torsion in adult rats. Int J Fertil Steril. 2022; 16(1): 30-35.
6. Akdemir A, Erbaş O, Ergenoğlu M, Yeniel AÖ, Oltulu F, Yavaşoğlu A, et al. Montelukast prevents ischaemia/reperfusion-induced ovarian damage in rats. Eur J Obstet Gynecol Reprod Biol. 2014; 173: 71-76.
7. Li C, Jackson RM. Reactive species mechanisms of cellular hypoxia-reoxygenation injury. Am J Physiol Cell Physiol. 2002; 282(2): C227-C241.
8. Prieto-Moure B, Lloris-Carsí JM, Barrios-Pitarque C, Toledo-Pereyra LH, Lajara-Romance JM, Berda-Antolí M, et al. Pharmacology of ischemia–reperfusion. Translational research considerations. J Invest Surg. 2016; 29(4): 234-249.
9. Karaçor T, Dogan Z, Elibol E, Bulbul M, Nacar M. Effects of iloprost on experimental ischemia and reperfusion injury in rat ovary. Biotech Histochem. 2020; 95(5): 373-380.
10. Kumtepe Y, Odabasoglu F, Karaca M, Polat B, Halici MB, Keles ON, et al. Protective effects of telmisartan on ischemia/reperfusion injury of rat ovary: biochemical and histopathologic evaluation. Fertil Steril. 2010; 93(4): 1299-1307.
11. Oral A, Odabasoglu F, Halici Z, Keles ON, Unal B, Coskun AK, et al. Protective effects of montelukast on ischemia-reperfusion injury in rat ovaries subjected to torsion and detorsion: biochemical and histopathologic evaluation. Fertil Steril. 2011; 95(4): 1360-1366.
12. El Khashab IH, Abdelsalam RM, Elbrairy AI, Attia AS. Chrysin attenuates global cerebral ischemic reperfusion injury via suppression of oxidative stress, inflammation and apoptosis. Biomed Pharmacother. 2019; 112: 108619.
13. Goes AT, Jesse CR, Antunes MS, Ladd FVL, Ladd AAL, Luchese C, et al. Protective role of chrysin on 6-hydroxydopamine-induced neurodegeneration a mouse model of Parkinson's disease: Involvement of neuroinflammation and neurotrophins. Chem Biol Interact. 2018; 279: 111-120.
14. Khan R, Khan AQ, Qamar W, Lateef A, Tahir M, Rehman MU, et al. Chrysin protects against cisplatin-induced colon. toxicity via amelioration of oxidative stress and apoptosis: probable role of p38MAPK and p53. Toxicol Appl Pharmacol. 2012; 258(3): 315-329.
15. Shokri F, Shokoohi M, Abadi ARR, Kalarestaghi H. The ameliorative effect of Galega officinalis extract on histological damages, oxidative stress induced by torsion-detorsion in adult rats’ ovarian. Int J Women's Health Reprod Sci. 2019; 7(1): 119-123.
16. Shokoohi M, Soltani M, Abtahi-Eivary S-H, Niazi V, Poor MJR, Ravaei H, et al. Effect of hydro–alcoholic extract of Olea europaea on apoptosis–related genes and oxidative stress in a rat model of torsion/detorsion–induced ovarian damage. Asian Pac J Reprod. 2019; 8(4): 148-156.
17. Bagheri-abassi F, Alavi H, Mohammadipour A, Motejaded F, Ebrahimzadeh-bideskan A. The effect of silver nanoparticles on apoptosis and dark neuron production in rat hippocampus. Iran J Basic Med Sci. 2015; 18(7): 644-648.
18. Abtahi-Eivari SH, Moghimian M, Soltani M, Shoorei H, Asghari R, Hajizadeh H, et al. The effect of Galega officinalis on hormonal and metabolic profile in a rat model of polycystic ovary syndrome. Int J Women's Health Reprod Sci. 2018; 6(3): 276-282.
19. Halestrap AP, Clarke SJ, Javadov SA. Mitochondrial permeability transition pore opening during myocardial reperfusion—a target for cardioprotection. Cardiovasc Res. 2004; 61(3): 372-385.
20. Zhu J, Yao K, Wang Q, Guo J, Shi H, Ma L, et al. Ischemic postconditioning-regulated miR-499 protects the rat heart against ischemia/reperfusion injury by inhibiting apoptosis through PDCD4. Cell Physiol Biochem. 2016; 39(6): 2364-2380.
21. Kalogeris T, Bao Y, Korthuis RJ. Mitochondrial reactive oxygen species: a double edged sword in ischemia/reperfusion vs preconditioning. Redox Biol. 2014; 2: 702-714.
22. Bakan V, Çıralık H, Tolun Fİ, Atlı Y, Mil A, Öztürk Ş. Protective effect of erythropoietin on torsion/detorsion injury in rat model. J Pediatr Surg. 2009; 44(10): 1988-1994.
23. Kurt RK, Dogan AC, Dogan M, Albayrak A, Kurt SN, Eren F, et al. Protective effect of colchicine on ovarian ischemia–reperfusion injury: an experimental study. Reprod Sci. 2015; 22(5): 545-550.
24. Ha SK, Moon E, Kim SY. Chrysin suppresses LPS-stimulated proinflammatory responses by blocking NF-κB and JNK activations in microglia cells. Neurosci Lett. 2010; 485(3): 143-147.
25. Zhao S, Liang M, Wang Y, Hu J, Zhong Y, Li J, et al. Chrysin suppresses vascular endothelial inflammation via inhibiting the NF-κB signaling pathway. J Cardiovasc Pharmacol Ther. 2019; 24(3): 278-287.
26. Carden DL, Granger DN. Pathophysiology of ischaemia–reperfusion injury. J Pathol. 2000; 190(3): 255-266.
27. Melekoglu R, Ciftci O, Eraslan S, Alan S, Basak N. The protective effects of glycyrrhetinic acid and chrysin against ischemia-reperfusion injury in rat ovaries. Biomed Res Int. 2018; 2018: 5421308.
28. Tsai SC, Chen CP, Su TH, Kau MM, Lu CC. Involvement of ERK phosphorylation in the prevention of ischemia-induced ovarian follicular depletion by stem cells. Chin J Physiol. 2010; 53(3): 167-177.
29. Soltani M, Moghimian M, Abtahi H, Shokoohi M. The protective effect of Matricaria chamomilla extract on histological damage and oxidative stress induced by Torsion/Detorsion in adult rat ovary. Int J Women's Health Reprod Sci. 2017; 5(3): 187-192.
30. Nikoletopoulou V, Markaki M, Palikaras K, Tavernarakis N. Crosstalk between apoptosis, necrosis and autophagy. Biochim Biophys Acta. 2013; 1833(12): 3448-3459.
31. Jan R. Understanding apoptosis and apoptotic pathways targeted cancer therapeutics. Adv Pharm Bull. 2019; 9(2): 205-218.
32. Wolter KG, Hsu YT, Smith CL, Nechushtan A, Xi XG, Youle RJ. Movement of Bax from the cytosol to mitochondria during apoptosis. J Cell Biol. 1997; 139(5): 1281-1292.
33. Sun Y, Gao Q, Wu N, Li SD, Yao JX, Fan WJ. Protective effects of dexmedetomidine on intestinal ischemia‑reperfusion injury. Exp Ther Med. 2015; 10(2): 647-652.
34. Ayan M, Tas U, Sogut E, Caylı S, Kaya H, Esen M, et al. Protective effect of thymoquinone against testicular torsion induced oxidative injury. Andrologia. 2016; 48(2): 143-151.
35. Dharma SJ, Kholkute SD, Nandedkar TD. Apoptosis in endometrium of mouse during estrous cycle. Indian J Exp Biol. 2001; 39(3): 218-222.
36. Annie L, Gurusubramanian G, Roy VK. Estrogen and progesterone dependent expression of visfatin/NAMPT regulates proliferation and apoptosis in mice uterus during estrous cycle. J Steroid Biochem Mol Biol. 2019; 185: 225-236.