Potential protective effect of astaxanthin on ovary ischemia-reperfusion injury

Document Type : Original Article

Authors

1 Kafkas University, Faculty of Medicine, Department of Histology and Embryology, Kars, Turkey

2 Erzincan Binali Yildirim University, Faculty of Medicine, Department of Histology and Embryology, Erzincan, Turkey

3 Ataturk University, Faculty of Medicine, Department of Histology and Embryology, Erzurum, Turkey

4 Ataturk University, Faculty of Pharmacy, Department of Pharmacology, Erzurum, Turkey

5 Alanya Alaaddin Keykubat University, Faculty of Medicine, Department of Histology and Embryology, Antalya, Turkey

Abstract

Objective(s): We thought that astaxanthin (ASX) might be a protective agent in oxidative stress damage that develops against ischemia and reperfusion injury in the rat ovary.
Materials and Methods: The experimental groups consisted of healthy, I (Ischemia), I+ASX50, I+ASX100, I/R (Ischemia/Reperfusion), I/R+ ASX50, and I/R+ ASX100. Vascular clamps were applied to the ovaries for 3 hr to induce ischemia. For the reperfusion groups, the clamps were opened and blood flow was restored to the ovaries for 3 hr. At the end of the experiment, biochemical, histopathological, and immunohistochemical analyses were made from the tissue samples taken.
Results: While MDA levels increased significantly in I and I/R groups, SOD levels decreased. It was found that ASX significantly decreased MDA levels and increased SOD activity in treatment groups depending on the dose. Caspase 3, IL-1 β, and IL-6 expressions were severely increased in ischemia and I/R groups, while the severity of I+ASX50 and I/R+ASX100 immunoreactivity was decreased. While severe hemorrhage areas were observed in I and IR groups, minimal hemorrhage areas were observed in the treatment groups, especially in I/R+ASX100 groups. In addition, inflammatory cells and necrotic cells in the I/R group were not observed in I/R+ASX50 and I/R+ASX100 groups.
Conclusion: As a result, it was determined that ASX has a strong protective role against oxidative damage in the treatment of ovarian ischemia-reperfusion injury.

Keywords


1. Huchon C, Fauconnier A. Adnexal torsion: a literature review. Eur J Obstet Gynecol Reprod Biol 2010; 150:8-12.
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. Geimanaite L, Trainavicius K. Ovarian torsion in children: Management and outcomes. J Pediatr Surg 2013; 48:1946-1953.
4. Halici Z, Karaca M, Keles ON, Borekci B, Odabasoglu F, Suleyman H, et al. Protective effects of amlodipine on ischemia-reperfusion injury of rat ovary: Biochemical and histopathologic evaluation. Fertil Steril 2008; 90:2408-2415.
5. Krishnan S, Kaur H, Bali J, Rao K. Ovarian torsion in infertility management - missing the diagnosis means losing the ovary: A high price to pay. J Hum Reprod Sci 2011; 4:39-42.
6. Lagana AS, Sofo V, Salmeri FM, Palmara VI, Triolo O, Terzic MM, et al. Oxidative stress during ovarian torsion in pediatric and adolescent patients: Changing the perspective of the disease. Int J Fertil Steril 2016; 9:416-423.
7. Lorenz RT, Cysewski GR. Commercial potential for haematococcus microalgae as a natural source of astaxanthin. Trends Biotechnol 2000; 18:160-167.
8. Hussein G, Sankawa U, Goto H, Matsumoto K, Watanabe H. Astaxanthin, a carotenoid with potential in human health and nutrition. J Nat Prod 2006; 69:443-449.
9. Zhang ZW, Xu XC, Liu T, Yuan S. Mitochondrion-permeable anti-oxidants to treat ros-burst-mediated acute diseases. Oxid Med Cell Longev 2016; 1-10.
10. Ambati RR, Phang SM, Ravi S, Aswathanarayana RG. Astaxanthin: sources, extraction, stability, biological activities and its commercial applications--a review. Mar Drugs 2014; 12:128-152.
11. Qiu X, Fu K, Zhao X, Zhang Y, Yuan Y, Zhang S, et al. Protective effects of astaxanthin against ischemia/reperfusion induced renal injury in mice. J Transl Med 2015; 13:28-37.
12. Otsuka T, Shimazawa M, Inoue Y, Nakano Y, Ojino K, Izawa H, et al. Astaxanthin protects against retinal damage: evidence from in vivo and in vitro retinal ischemia and reperfusion models. Curr Eye Res 2016; 41:1465-1472.
13. Li S, Takahara T, Fujino M, Fukuhara Y, Sugiyama T, Li XK, et al. Astaxanthin prevents ischemia-reperfusion injury of the steatotic liver in mice. PLoS One 2017; 12:1-16.
14. Yayla M, Cetin D, Adali Y, Kilicle PA, Toktay E. Potential therapeutic effect of pomegranate seed oil on ovarian ischemia/reperfusion injury in rats. Iran J Basic Med Sci 2018; 21:1262-1268.
15. Li X, Qi Z, Zhao L, Yu Z. Astaxanthin reduces type 2 diabeticassociated cognitive decline in rats via activation of PI3K/Akt and attenuation of oxidative stress. Mol Med Rep 2016; 13:973-979.
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. Cadirci E, Halici Z, Yayla M, Toktay E, Bayir Y, Karakus E, et al. Blocking of urotensin receptors as new target for treatment of carrageenan induced inflammation in rats. Peptides 2016; 82:35-43.
18. Choudhury KR, Yagle KJ, Swanson PE, Krohn KA, Rajendran JG. A robust automated measure of average sntibody staining in immunohistochemistry images. J Histochem Cytochem 2010; 58:95-107.
19. Klein M, Vignaud JM, Hennequin V, Toussaint B, Bresler L, Plenat F, et al. Increased expression of the vascular endothelial growth factor is a pejorative prognosis marker in papillary thyroid carcinoma. J Clin Endocrinol Metab 2001; 86:656-658.
20. Ural DA, Aykan DA, Koçarslan S, Doğaner A. Effect of tadalafil treatment on ovarian ischemia injury in rats. Cukurova Med J 2021; 46:55-62.
21. 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.
22. Kalogeris T, Baines CP, Krenz M, Korthuis RJ. Cell biology of ischemia/reperfusion injury. Int Rev Cell Mol Biol 2012; 298:229-317.
23. Siesjo BK. Historical overview. calcium, ischemia, and death of brain cells. Ann N Y Acad Sci 1988; 522:638-661.
24. Hatanaka N, Kamike W, Shimizu S, Miyata M, Inoue T, Yoshida Y, et al. Ca2+ release from mitochondria induces cytosolic enzyme leakage in anoxic liver. J Surg Res 1995; 58:485-490.
25. Mangino MJ, Anderson CB, Murphy MK, Brunt E, Turk J. Mucosal arachidonate metabolism and intestinal ischemia-reperfusion injury. Am J Physiol 1989; 257:299-307.
26. Miki W. Biological functions and activities of animal carotenoids. Pure Appl Chem 1991; 63:141-146.
27. Higuera-Ciapara I, Felix-Valenzuela L, Goycoolea F. Astaxanthin: a review of its chemistry and applications. Crit Rev Food Sci Nutr 2006; 46:185-196.
28. Sztretye M, Dienes B, Gonczi M, Czirjak T, Csernoch L, Dux L, et al. Astaxanthin: a potential mitochondrial-targeted anti-oxidant treatment in diseases and with aging. Oxid Med Cell Longev 2019; 1-14.
29. Wu H, Niu H, Shao A, Wu C, Dixon BJ, Zhang J, et al. Astaxanthin as a potential neuroprotective agent for neurological diseases. Mar Drugs 2015; 13:5750-5766.
30. Sun SQ, Zhao YX, Li SY, Qiang JW, Ji YZ. Anti-tumor effects of astaxanthin by inhibition of the expression of STAT3 in prostate cancer. Mar Drugs 2020; 18:415-428.
31. Liu H, Liu M, Fu X, Zhang Z, Zhu L, Zheng X, et al. Astaxanthin prevents alcoholic fatty liver disease by modulating mouse gut microbiota. Nutrients 2018; 10:1298-1315.
32. Lobo V, Patil A, Phatak A, Chandra N. Free radicals, antioxidants and functional foods: impact on human health. Pharmacogn Rev 2010; 4:118-126.
33. Fassett RG, Coombes JS. Astaxanthin, oxidative stress, inflammation and cardiovascular disease. Future Cardiol 2009; 5:333-342.
34. Younus H. Therapeutic potentials of superoxide dismutase. Int J Health Sci (Qassim) 2018; 12:88-93.
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. Islam MA, Al Mamun MA, Faruk M, Ul Islam MT, Rahman MM, Alam MN, et al. Astaxanthin ameliorates hepatic damage and oxidative stress in carbon tetrachloride-administered rats. Pharmacognosy Res 2017; 9:84-91.
37. Topcu A, Balik G, Atak M, Mercantepe T, Uydu HA, Tumkaya L. An investigation of the effects of metformin on ovarian ischemia-reperfusion injury in rats. Eur J Pharmacol 2019; 865:172790-172800.
38. Ozlem K, Birkan Y, Mustafa K, Emin K. Protective effect of Vaccinium myrtillus on ischemia- reperfusion injury in rat ovary. Taiwan J Obstet Gynecol 2018; 57:836-841.
39. Karacor T, Dogan Z, Elibol E, Bulbul M, Nacar MC. Effects of iloprost on experimental ischemia and reperfusion injury in rat ovary. Biotech Histochem 2020; 95:373-380.
40. Geyikoglu F, Koc K, Erol HS, Colak S, Ayer H, Jama S, et al. The propolis and boric acid can be highly suitable, alone/or as a combinatory approach on ovary ischemia-reperfusion injury. Arch Gynecol Obstet 2019; 300:1405-1412.
41. Carlson NG, Wieggel WA, Chen J, Bacchi A, Rogers SW, Gahring LC. Inflammatory cytokines IL-1 alpha, IL-1 beta, IL-6, and TNF-alpha impart neuroprotection to an excitotoxin through distinct pathways. J Immunol 1999; 163:3963-3968.
42. Priyadarshini L, Aggarwal A. Astaxanthin inhibits cytokines production and inflammatory gene expression by suppressing IkappaB kinase-dependent nuclear factor kappaB activation in pre and postpartum murrah buffaloes during different seasons. Vet World 2018; 11:782-788.
43. Kim YH, Koh HK, Kim DS. Down-regulation of IL-6 production by astaxanthin via ERK-, MSK-, and NF-kappaB-mediated signals in activated microglia. Int Immunopharmacol 2010; 10:1560-1572.
44. Elmore S. Apoptosis: A review of programmed cell death. Toxicol Pathol 2007; 35:495-516.
45. 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.