DOI QR코드

DOI QR Code

The effects of berberine on ischemia-reperfusion injuries in an experimental model of ovarian torsion

  • Filiz Yilmaz (Department of Histology and Embryology, Hitit University, Erol Olcok Research and Training Hospital, IVF Center) ;
  • Orkun Ilgen (Department of Obstetrics and Gynecology, Erzurum Research and Training Hospital) ;
  • Alper Mankan (Department of Obstetrics and Gynecology, Dokuz Eylul University, Faculty of Medicine) ;
  • Bayram Yilmaz (Pathology Department, Training and Research Hospital, Hitit University) ;
  • Sefa Kurt (Department of Obstetrics and Gynecology, Dokuz Eylul University, Faculty of Medicine)
  • 투고 : 2023.07.18
  • 심사 : 2023.08.31
  • 발행 : 2023.12.31

초록

Objective: Ovarian torsion is a gynecological disorder that causes ischemia-reperfusion injuries in the ovary. Our study investigated berberine's short- and long-term effects on ovarian ischemia-reperfusion injuries. Methods: This study included 28 Wistar albino female rats weighing 180 to 220 g, which were divided into four groups: sham (S), torsion/detorsion (T/D), torsion/ detorsion+single dose berberine (T/D+Bb), and torsion/detorsion+15 days berberine (T/D+15Bb). The torsion and detorsion model was applied in all non-sham groups. In the T/D+Bb group, a single dose of berberine was administered, while in the T/D+15Bb group, berberine was administered over a period of 15 days. After the rats were euthanized, their ovaries were excised. The left ovaries were used for histopathologic evaluation, which included ovarian injury scoring and follicle count, while the right ovaries were used for biochemical analyses (tissue transforming growth factor-β [TGF-β] and alpha-smooth muscle actin [α-SMA] levels). Results: The histopathologic evaluation scores for the ovaries were significantly lower in the T/D+B group (p<0.05) and the T/D+15B group (p<0.005) than in the T/D group. The follicle counts in the T/D group were lower than those in both the sham and treated groups (p<0.005). The TGF-β levels were significantly lower in the T/D+15B group (p<0.005), whereas the α-SMA levels did not show a significant difference. Conclusion: Both short- and long-term berberine use could potentially have therapeutic effects on ovarian torsion. Long-term berberine use exhibited anti-inflammatory effects by reducing TGF-β levels, thereby preventing ischemia-reperfusion injuries. Therefore, we suggest that long-term berberine use could be beneficial for ovarian torsion.

키워드

참고문헌

  1. Huchon C, Fauconnier A. Adnexal torsion: a literature review. Eur J Obstet Gynecol Reprod Biol 2010;150:8-12. https://doi.org/10.1016/j.ejogrb.2010.02.006
  2. Halladin NL. Oxidative and inflammatory biomarkers of ischemia and reperfusion injuries. Dan Med J 2015;62:B5054.
  3. Turk E, Karaca I, Ozcinar E, Celebiler A, Aybek H, Ortac R, et al. The effect of hypothermia on adnexal torsion/detorsion injury in a rat ovary model. J Pediatr Surg 2015;50:1378-81. https://doi.org/10.1016/j.jpedsurg.2015.01.011
  4. Sagsoz N, Kisa U, Apan A. Ischaemia-reperfusion injury of rat ovary and the effects of vitamin C, mannitol and verapamil. Hum Reprod 2002;17:2972-6. https://doi.org/10.1093/humrep/17.11.2972
  5. Dokuyucu R, Karateke A, Gokce H, Kurt RK, Ozcan O, Ozturk S, et al. Antioxidant effect of erdosteine and lipoic acid in ovarian ischemia-reperfusion injury. Eur J Obstet Gynecol Reprod Biol 2014;183:23-7. https://doi.org/10.1016/j.ejogrb.2014.10.018
  6. 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;44:1988-94. https://doi.org/10.1016/j.jpedsurg.2009.02.071
  7. Yurtcu E, Togrul C, Ozyer S, Uzunlar O, Karatas YH, Seckin KD, et al. Dose dependent protective effects of vardenafil on ischemiareperfusion injury with biochemical and histopathologic evaluation in rat ovary. J Pediatr Surg 2015;50:1205-9. https://doi.org/10.1016/j.jpedsurg.2014.12.013
  8. Sak ME, Soydinc HE, Sak S, Evsen MS, Alabalik U, Akdemir F, et al. The protective effect of curcumin on ischemia-reperfusion injury in rat ovary. Int J Surg 2013;11:967-70. https://doi.org/10.1016/j.ijsu.2013.06.007
  9. Komal S, Ranjan B, Neelam C, Birendra S, Kumar SN. Berberis aristata: a review. Int J Res Ayurveda Pharm 2011;2:383-8.
  10. Singh J, Kakkar P. Antihyperglycemic and antioxidant effect of Berberis aristata root extract and its role in regulating carbohydrate metabolism in diabetic rats. J Ethnopharmacol 2009;123:22-6. https://doi.org/10.1016/j.jep.2009.02.038
  11. Birdsall TC, Kelly GS. Berberine: therapeutic potential of an alkaloid found in several medicinal plants. Altern Med Rev 1997;2:94-103.
  12. Battu SK, Repka MA, Maddineni S, Chittiboyina AG, Avery MA, Majumdar S. Physicochemical characterization of berberine chloride: a perspective in the development of a solution dosage form for oral delivery. AAPS PharmSciTech 2010;11:1466-75. https://doi.org/10.1208/s12249-010-9520-y
  13. Bhutada P, Mundhada Y, Bansod K, Dixit P, Umathe S, Mundhada D. Anticonvulsant activity of berberine, an isoquinoline alkaloid in mice. Epilepsy Behav 2010;18:207-10. https://doi.org/10.1016/j.yebeh.2010.03.007
  14. Kulkarni SK, Dhir A. Berberine: a plant alkaloid with therapeutic potential for central nervous system disorders. Phytother Res 2010;24:317-24. https://doi.org/10.1002/ptr.2968
  15. Domitrovic R, Cvijanovic O, Pernjak-Pugel E, Skoda M, Mikelic L, Crncevic-Orlic Z. Berberine exerts nephroprotective effect against cisplatin-induced kidney damage through inhibition of oxidative/nitrosative stress, inflammation, autophagy and apoptosis. Food Chem Toxicol 2013;62:397-406. https://doi.org/10.1016/j.fct.2013.09.003
  16. Li J, Pan Y, Kan M, Xiao X, Wang Y, Guan F, et al. Hepatoprotective effects of berberine on liver fibrosis via activation of AMP-activated protein kinase. Life Sci 2014;98:24-30. https://doi.org/10.1016/j.lfs.2013.12.211
  17. Othman MS, Safwat G, Aboulkhair M, Abdel Moneim AE. The potential effect of berberine in mercury-induced hepatorenal toxicity in albino rats. Food Chem Toxicol 2014;69:175-81. https://doi.org/10.1016/j.fct.2014.04.012
  18. Li MH, Zhang YJ, Yu YH, Yang SH, Iqbal J, Mi QY, et al. Berberine improves pressure overload-induced cardiac hypertrophy and dysfunction through enhanced autophagy. Eur J Pharmacol 2014;728:67-76. https://doi.org/10.1016/j.ejphar.2014.01.061
  19. Kazaz IO, Mentese A, Demir S, Kerimoglu G, Colak F, Bodur A, et al. Berberine inhibits the ischemia-reperfusion induced testicular injury through decreasing oxidative stress. Am J Emerg Med 2020;38:33-7. https://doi.org/10.1016/j.ajem.2019.04.001
  20. Kumas M, Esrefoglu M, Karatas E, Duymac N, Kanbay S, Ergun IS, et al. Investigation of dose-dependent effects of berberine against renal ischemia/reperfusion injury in experimental diabetic rats. Nefrologia (Engl Ed) 2019;39:411-23. https://doi.org/10.1016/j.nefroe.2019.08.002
  21. Guile SL, Mathai JK. Ovarian torsion. In: StatPearls [Internet]. StatPearls Publishing; 2023 [cited 2023 Oct 2]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK560675
  22. 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;181:240-5. https://doi.org/10.1016/j.ejogrb.2014.08.001
  23. Ozler A, Turgut A, Soydinc HE, Sak ME, Evsen MS, Alabalik U, et al. The biochemical and histologic effects of adnexal torsion and early surgical intervention to unwind detorsion on ovarian reserve: an experimental study. Reprod Sci 2013;20:1349-55. https://doi.org/10.1177/1933719113485300
  24. Chang W, Zhang M, Li J, Meng Z, Xiao D, Wei S, et al. Berberine attenuates ischemia-reperfusion injury via regulation of adenosine-5'-monophosphate kinase activity in both non-ischemic and ischemic areas of the rat heart. Cardiovasc Drugs Ther 2012;26:467-78. https://doi.org/10.1007/s10557-012-6422-0
  25. Ilgen O, Hortu I, Ozceltik G, Yigitturk G, Erbas O, Karadadas N. Effects of methylene blue on ovarian torsion-detorsion injury in a rat model. J Pediatr Adolesc Gynecol 2020;33:506-10. https://doi.org/10.1016/j.jpag.2020.06.010
  26. Hortu I, Ilgen O, Sahin C, Akdemir A, Yigitturk G, Erbas O. Losartan ameliorates ovarian ischaemia/reperfusion injury in rats: an experimental study. J Obstet Gynaecol 2020;40:1148-54. https://doi.org/10.1080/01443615.2019.1701639
  27. Parlakgumus HA, Aka Bolat F, Bulgan Kilicdag E, Simsek E, Parlakgumus A. Atorvastatin for ovarian torsion: effects on follicle counts, AMH, and VEGF expression. Eur J Obstet Gynecol Reprod Biol 2014;175:186-90. https://doi.org/10.1016/j.ejogrb.2014.01.017
  28. Karakas S, Kaya C, Guraslan H, Sakiz D, Suzen Caypinar S, Cengiz H, et al. Effect of metformin and detorsion treatment on serum anti-Mullerian hormonelevels and ovarian histopathology in a rat ovarian torsion model. Turk J Med Sci 2020;50:455-63.
  29. Kaya C, Turgut H, Cengiz H, Turan A, Ekin M, Yasar L. Effect of detorsion alone and in combination with enoxaparin therapy on ovarian reserve and serum antimullerian hormone levels in a rat ovarian torsion model. Fertil Steril 2014;102:878-84. https://doi.org/10.1016/j.fertnstert.2014.06.007
  30. Topcu A, Balik G, Atak M, Mercantepe T, Uydu HA, Tumkaya L. An investigation of the effects of metformin on ovarian ischemiareperfusion injury in rats. Eur J Pharmacol 2019;865:172790.
  31. Topcu A, Ozturk A, Deniz E, Duman Ozturk S, Arpa M, Atak M. The effects of amiodarone in ovarian injury due to oxidative stress and inflammation caused by ischemia-reperfusion. Immunopharmacol Immunotoxicol 2022;44:1022-31. https://doi.org/10.1080/08923973.2022.2102991
  32. Kalyoncu S, Yilmaz B, Demir M, Tuncer M, Bozdag Z, Ince O, et al. Octreotide and lanreotide decrease ovarian ischemia-reperfusion injury in rats by improving oxidative and nitrosative stress. J Obstet Gynaecol Res 2020;46:2050-8. https://doi.org/10.1111/jog.14379
  33. Lewis KD, Falk M. Toxicological assessment of dihydroberberine. Food Chem Toxicol 2022;168:113301.
  34. Ilgen O, Hortu I, Ozceltik G, Yigitturk G, Erbas O, Karadadas N. Effects of methylene blue on ovarian torsion-detorsion injury in a rat model. J Pediatr Adolesc Gynecol 2020;33:506-10. https://doi.org/10.1016/j.jpag.2020.06.010
  35. Uzun O, Kaban I, Midi A, Uysal H, Boran AB, Bacanakgil BH, et al. Diagnostic value of signal peptide-CUB-EGF domain-containing protein 1 as an early and late biochemical marker in the ovarian torsion rat model. J Obstet Gynaecol Res 2018;44:1092-9. https://doi.org/10.1111/jog.13630
  36. Wang Z, Nie K, Su H, Tang Y, Wang H, Xu X, et al. Berberine improves ovulation and endometrial receptivity in polycystic ovary syndrome. Phytomedicine 2021;91:153654.
  37. Zhu L, Gu P, Shen H. Protective effects of berberine hydrochloride on DSS-induced ulcerative colitis in rats. Int Immunopharmacol 2019;68:242-51. https://doi.org/10.1016/j.intimp.2018.12.036
  38. Eken MK, Ersoy GS, Kaygusuz EI, Devranoglu B, Takir M, Cilingir OT, et al. Etanercept protects ovarian reserve against ischemia/reperfusion injury in a rat model. Arch Med Sci 2019;15:1104-12. https://doi.org/10.5114/aoms.2017.72406
  39. Xue W, Xue F, Jia T, Hao A. Research and experimental verification of the molecular mechanism of berberine in improving premature ovarian failure based on network pharmacology. Bioengineered 2022;13:9885-900. https://doi.org/10.1080/21655979.2022.2062104
  40. Deger U, Cavus Y. Investigation of the role of rosmarinic acid treatment in regulating inflammation, cell damage, and angiogenesis in rat ovarian torsion and detorsion models. Acta Cir Bras 2020;35:e202000304.
  41. Nayki C, Nayki U, Keskin Cimen F, Kulhan M, Yapca OE, Kurt N, et al. The effect of rutin on ovarian ischemia-reperfusion injury in a rat model. Gynecol Endocrinol 2018;34:809-14. https://doi.org/10.1080/09513590.2018.1450378
  42. Putra A, Alif I, Hamra N, Santosa O, Kustiyah AR, Muhar AM, et al. MSC-released TGF-β regulate α-SMA expression of myofibroblast during wound healing. J Stem Cells Regen Med 2020;16:73-9. https://doi.org/10.46582/jsrm.1602011
  43. Shinde AV, Humeres C, Frangogiannis NG. The role of α-smooth muscle actin in fibroblast-mediated matrix contraction and remodeling. Biochim Biophys Acta Mol Basis Dis 2017;1863:298-309. https://doi.org/10.1016/j.bbadis.2016.11.006