Protective effects of glutathione administration on ischemia-reperfusion injury in rat ovaries

Abstract

We aimed to examine the biochemical and histopathological potential beneficial effects of glutathione administration on the ovarian ischemia/reperfusion injury (IRI) model. Thirty Wistar Albino female rats were used in this experimental study and were divided into five groups. Group 1 (sham) underwent observational laparotomy. Group 2 (torsion) had their left ovaries torsioned. Group 3 (torsion + detorsion) was detorsioned after torsion. Groups 4 and 5 received the same procedure as group 3. 0,2 ml glutathione was applied to the left ovaries of group 4 (torsion + detorsion + intraovarian glutathione injection) after detorsion. Group 5 (torsion + detorsion + intraperitoneal glutathione injection) was administered 1 ml glutathione intraperitoneally five times. Fifteenth-day blood samples were taken to examine total antioxidant status, total oxidant status, oxidative stress index, anti-mullerian hormone (AMH), and malondialdehyde (MDA) values. Besides, the left ovaries were resected for histopathological examination. Total antioxidant status was significantly higher in the intraperitoneal injection group (p<0.05). The AMH values of the sham and intraovarian groups were similar (p>0.05). MDA value did not differ significantly between the sham, intraovarian, and intraperitoneal injection groups (p>0.05). In histopathological examination, no significant benefit of glutathione application on follicle numbers was shown. The main limitations of our study were the relatively small size of our series, the absence of serial blood measurement, the absence of a group in which intraovarian and intraperitoneal injections were administered together, and the absence of a sham + drug group. Glutathione administration reduces the detrimental effects of ovarian IRI.

Keywords

• Anti-Mullerian Hormone
• Glutathione
• Ischemia Reperfusion Injury
• Ovarian Torsion

References

1. 1. Oelsner G, Shashar D. Adnexal torsion. Clin Obstet Gynecol. 2006 Sep;49(3):459-63. doi: 10.1097/00003081-200609000-00006. PMID: 16885653.
2. 2. White M, Stella J. Ovarian torsion: 10-year perspective. Emerg Med Australas. 2005 Jun;17(3):231-7. doi: 10.1111/j.1742-6723.2005.00728.x. PMID: 15953224.
3. 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 Mar;24(3):315-8. doi: 10.1007/s00383-007-2079-3. Epub 2007 Nov 30. PMID: 18060415.
4. 4. Anders JF, Powell EC. Urgency of evaluation and outcome of acute ovarian torsion in pediatric patients. Arch Pediatr Adolesc Med. 2005 Jun;159(6):532-5. doi: 10.1001/archpedi.159.6.532. PMID: 15939851.
5. 5. Borekci B, Gundogdu C, Altunkaynak BZ, Calık M, Altunkaynak ME, Unal D, Unal B. The protective effect of dehydroepiandrosterone on ovarian tissues after torsion-detorsion injury: a stereological and histopathological study. Eurasian J Med. 2009 Apr;41(1):22-7. PMID: 25610059; PMCID: PMC4261661.
6. 6. Kabay S, Ozden H, Guven G, Burukoglu D, Ustuner MC, Topal F, Gunes HV, Ustuner D, Ozbayer C. Protective effects of the nuclear factor kappa B inhibitor pyrrolidine dithiocarbamate on experimental testicular torsion and detorsion injury. Korean J Physiol Pharmacol. 2014 Aug;18(4):321-6. doi: 10.4196/kjpp.2014.18.4.321. Epub 2014 Aug 13. PMID: 25177164; PMCID: PMC4146634.
7. 7. Li C, Jackson RM. Reactive species mechanisms of cellular hypoxia-reoxygenation injury. Am J Physiol Cell Physiol. 2002 Feb;282(2):C227-41. doi: 10.1152/ajpcell.00112.2001. PMID: 11788333.
8. 8. Jung JE, Kim GS, Chen H, Maier CM, Narasimhan P, Song YS, Niizuma K, Katsu M, Okami N, Yoshioka H, Sakata H, Goeders CE, Chan PH. Reperfusion and neurovascular dysfunction in stroke: from basic mechanisms to potential strategies for neuroprotection. Mol Neurobiol. 2010 Jun;41(2-3):172-9. doi: 10.1007/s12035-010-8102-z. Epub 2010 Feb 17. PMID: 20157789; PMCID: PMC2877155.

9. 9. Cure MC, Cure E, Kalkan Y, Tumkaya L, Aydin I, Kirbas A, Efe H, Kurt A, Yuce S. The Protective Effect of Adalimumab on Renal Injury in a Model of Abdominal Aorta Cross-Clamping. Adv Clin Exp Med. 2016 Mar-Apr;25(2):219-26. doi: 10.17219/acem/33250. PMID: 27627553.
10. 10. Ayala A, Muñoz MF, Argüelles S. Lipid peroxidation: production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal. Oxid Med Cell Longev. 2014;2014:360438. doi: 10.1155/2014/360438. Epub 2014 May 8. PMID: 24999379; PMCID: PMC4066722.
11. 11. Pizzorno J. Glutathione! Integr Med (Encinitas). 2014 Feb;13(1):8-12. PMID: 26770075; PMCID: PMC4684116.
12. 12. Minich DM, Brown BI. A Review of Dietary (Phyto)Nutrients for Glutathione Support. Nutrients. 2019 Sep 3;11(9):2073. doi: 10.3390/nu11092073. PMID: 31484368; PMCID: PMC6770193.
13. 13. Mukherjee A, Malik H, Saha AP, Dubey A, Singhal DK, Boateng S, Saugandhika S, Kumar S, De S, Guha SK, Malakar D. Resveratrol treatment during goat oocytes maturation enhances developmental competence of parthenogenetic and hand-made cloned blastocysts by modulating intracellular glutathione level and embryonic gene expression. J Assist Reprod Genet. 2014 Feb;31(2):229-39. doi: 10.1007/s10815-013-0116-9. Epub 2013 Dec 4. PMID: 24305840; PMCID: PMC3933608.
14. 14. Kankofer M, Wawrzykowski J, Giergiel M. Sex- and age-dependent activity of glutathione peroxidase in reproductive organs in pre- and post-pubertal cattle in relation to total antioxidant capacity. Aging Clin Exp Res. 2013 Aug;25(4):365-70. doi: 10.1007/s40520-013-0056-3. Epub 2013 Jun 6. PMID: 23740597.
15. 15. Lim J, Lawson GW, Nakamura BN, Ortiz L, Hur JA, Kavanagh TJ, Luderer U. Glutathione-deficient mice have increased sensitivity to transplacental benzo[a]pyrene-induced premature ovarian failure and ovarian tumorigenesis. Cancer Res. 2013 Jan 15;73(2):908-17. doi: 10.1158/0008-5472.CAN-12-3636. Epub 2012 Nov 7. PMID: 23135907; PMCID: PMC3548973.
16. 16. Schauer RJ, Gerbes AL, Vonier D, Meissner H, Michl P, Leiderer R, Schildberg FW, Messmer K, Bilzer M. Glutathione protects the rat liver against reperfusion injury after prolonged warm ischemia. Ann Surg. 2004 Feb;239(2):220-31. doi: 10.1097/01.sla.0000110321.64275.95. PMID: 14745330; PMCID: PMC1356215.
17. 17. Schauer RJ, Kalmuk S, Gerbes AL, Leiderer R, Meissner H, Schildberg FW, Messmer K, Bilzer M. Intravenous administration of glutathione protects parenchymal and non-parenchymal liver cells against reperfusion injury following rat liver transplantation. World J Gastroenterol. 2004 Mar 15;10(6):864-70. doi: 10.3748/wjg.v10.i6.864. PMID: 15040034; PMCID: PMC4726997.
18. 18. Cavaletti G, Minoia C, Schieppati M, Tredici G. Protective effects of glutathione on cisplatin neurotoxicity in rats. Int J Radiat Oncol Biol Phys. 1994 Jul 1;29(4):771-6. doi: 10.1016/0360-3016(94)90565-7. PMID: 8040023.
19. 19. Bilommi R, Nawas BA, Kusmayadi DD, Diposarosa R, Chairul A, Hernowo BS. The effects of glutathione on malondialdehyde expression and seminiferous tubule damage in experimental testicular torsion-detorsion in Wistar rats. J Pediatr Urol. 2013 Dec;9(6 Pt B):1059-63. doi: 10.1016/j.jpurol.2013.03.008. Epub 2013 Apr 17. PMID: 23602206.
20. 20. Gardiner CS, Salmen JJ, Brandt CJ, Stover SK. Glutathione is present in reproductive tract secretions and improves development of mouse embryos after chemically induced glutathione depletion. Biol Reprod. 1998 Aug;59(2):431-6. doi: 10.1095/biolreprod59.2.431. PMID: 9687318.
21. 21. Female reproductive system. Young B, Heath WJ, editors. Wheater’s Functional Histology: a text and colour atlas. fourth ed., Sydney: Churchill Livingstone; 2000.
22. 22. Erel O. A novel automated method to measure total antioxidant response against potent free radical reactions. Clin Biochem. 2004 Feb;37(2):112-9. doi: 10.1016/j.clinbiochem.2003.10.014. PMID: 14725941.
23. 23. Erel O. A new automated colorimetric method for measuring total oxidant status. Clin Biochem. 2005 Dec;38(12):1103-11. doi: 10.1016/j.clinbiochem.2005.08.008. Epub 2005 Oct 7. PMID: 16214125.
24. 24. Ozler A, Turgut A, Görük NY, Alabalik U, Basarali MK, Akdemir F. Evaluation of the protective effects of CoQ₁₀ on ovarian I/R injury: an experimental study. Gynecol Obstet Invest. 2013;76(2):100-6. doi: 10.1159/000353425. Epub 2013 Jul 23. PMID: 23886769.
25. 25. Fujii J, Iuchi Y, Okada F. Fundamental roles of reactive oxygen species and protective mechanisms in the female reproductive system. Reprod Biol Endocrinol. 2005 Sep 2;3:43. doi: 10.1186/1477-7827-3-43. PMID: 16137335; PMCID: PMC1224869.
26. 26. Girotti AW. Lipid hydroperoxide generation, turnover, and effector action in biological systems. J Lipid Res. 1998 Aug;39(8):1529-42. PMID: 9717713.
27. 27. Celik Kavak E, Gulcu Bulmus F, Bulmus O, Kavak SB, Kocaman N. Magnesium: does it reduce ischemia/reperfusion injury in an adnexal torsion rat model? Drug Des Devel Ther. 2018 Feb 28;12:409-415. doi: 10.2147/DDDT.S157115. PMID: 29535502; PMCID: PMC5836654.
28. 28. La Marca A, Sighinolfi G, Radi D, Argento C, Baraldi E, Artenisio AC, Stabile G, Volpe A. Anti-Mullerian hormone (AMH) as a predictive marker in assisted reproductive technology (ART). Hum Reprod Update. 2010 Mar-Apr;16(2):113-30. doi: 10.1093/humupd/dmp036. Epub 2009 Sep 30. PMID: 19793843.
29. 29. Calis P, Bozdag G, Karakoc Sokmensuer L, Kender N. Does ischemia-reperfusion injury affect ovarian reserve and follicle viability in a rat model with adnexal torsion? Eur J Obstet Gynecol Reprod Biol. 2015 Feb;185:126-30. doi: 10.1016/j.ejogrb.2014.12.006. Epub 2014 Dec 23. PMID: 25575140.