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Effect of tadalafil treatment on ovarian ischemia injury in rats

Year 2021, Volume: 46 Issue: 1, 55 - 62, 31.03.2021

Abstract

Purpose: Ovarian ischemia, which is known as one of the most common gynecologic surgery emergencies in women of all ages, is the distruption of the ovarian perfusion. Herein, we aimed to investigate the effect of tadalafil, a phosphodiesterase-5 inhibitor, at different doses and durations in the management of ovarian survival in ischemia-reperfusion injury model in rats. Materials and Materials and Methods: Thirty female Wistar albino rats were divided into five groups. Ovarian ischemia was induced by clamping the adnex of uterine tuba for three hours and reperfused for one hour. Drug treatments were given as follows: Group 1: saline (ischemic control), Group 2: tadalafil 1 mg/kg, Group 3: tadalafil 10 mg/kg, Group 4: tadalafil 1 mg/kg for 7 days, Group 5: tadalafil 10 mg/kg for 7 days. At the end of the treatments, ovaries were removed and evaluated for histopathological analysis. Results: Group 4 and Group 5 showed significant decrease in vascular congesion, hemorrhage, edema, neutrophilic infiltration compared to Group 1. All groups showed significant decrease in neutrophilic infiltration compared to Group 1. We found that treatment with tadalafil for 7 days significantly decreased the ovarian tissue damage scores in rats compared to the ischemic control.
Conclusion: Our results showed that tadalafil treatment in ischemic ovarian injury is effective in limiting ovarian damage. The reduction in the tissue damage scores suggested that treatment with PDE5 inhibitors, such as tadalafil, may contribute to the healing of conservatively treated ovaries and may play a role in the treatment of adnexal torsion.

References

  • 1. Erturk N, Elbe H, Erdemli ME, Aktas S, Yigitturk G, Aksungur Z, Suzen A, et al. Protective effects of sildenafil and resveratrol on ovarian ischemiareperfusion injury in rats. Biomedical Research 2017; 28: 9113-20.
  • 2. Laganà AS, Sofo V, Salmeri FM, Palmara VI, Triolo O, Terzić MM, Patrelli TS, et al. Oxidative Stress during Ovarian Torsion in Pediatric and Adolescent Patients: Changing The Perspective of The Disease. Int J Fertil Steril. 2016; 9: 416-23.
  • 3. Isik A, Peker K, Gursul C, Sayar I, Firat D, Yilmaz I, Demiryilmaz I. The effect of ozone and naringin on intestinal ischemia/reperfusion injury in an experimental model, International Journal of Surgery. 2015; 21: 38e4439.
  • 4. Dasgupta R, Renaud E, Goldin AB, Baird R, Cameron DB, Arnold MA, DiefenbachKA, et al. Ovarian torsion inpediatric and adolescent patients: A systematic review. J Pediatr Surg. 2018; 53: 1387-91.
  • 5. Childress KJ, Dietrich JE. Pediatric Ovarian Torsion. Surg Clin North Am. 2017; 97: 209-21.
  • 6. Yildirim N, Simsek D, Kose S, Yildirim AGS, Guven C, Yigitturk G, Erbas O. The protective effect of Gingko biloba in a rat model of ovarian ischemia/reperfusion injury: Improvement in histological and biochemical parameters. Adv Clin Exp Med. 2018; 27: 591-7.
  • 7. Çılgın H, Şimşek M, Bal R. Can adnexal torsion be predicted by measuringplasma heat shock protein 70 level? An experimental study. Arch Gynecol Obstet.2017; 296: 941-6.
  • 8.Altintas Aykan D.,Yaman S. Tadalafil exerts a dual effect in behavioral pain responses in rats. Ann Med Res 2020; 27: 749-54.
  • 9. Wietzikoski EGG, Foiatto JC, Czeczko NG, Malafaia O, Koleski FC, Mierzwa TC, Gomes RPX. Tadalafil protector effect during ischemia-reperfusion in rats. Acta Cir Bras. 2017; 32: 973-83.
  • 10 . Gasanov F, Aytac B, Vuruskan H. The effects of tadalafil on renal ischemia reperfusion injury: an experimental study. Bosn J Basic Med Sci. 2011; 11: 158-62.
  • 11.Ural A, Bilgen F, Altıntaş Aykan D, Bahar AY, Bekerecioğlu M, Altıntaş Ural D. Effects of dabigatran and fondaparinux on degloving injuries: An experimental study. Ulus Travma Acil Cerrahi Derg 2020; 26: 343-50.
  • 12. Farnaz Shokri, Majid Shokoohi, Ayda Roudi Rasht Abadi, Hossein Kalarestaghi. The ameliorative effect of Galega officinalis extract on histological damages, oxidative stress induced by torsion-detorsion in adult rats’ ovarian, Int J Womens Health Reprod Sci. 2019; 7; 119-23.
  • 13. 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.
  • 14. Balasubramaniam D, Duraisamy KY, Ezhilmani M. Laparoscopic Detorsion andFertility Preservation in Twisted Ischemic Adnexa - A Single-Center Prospective Study. Gynecol Minim Invasive Ther. 2020; 9: 24-8.
  • 15. Refaie MMM, El-Hussieny M. Protective effect of pioglitazone on ovarian ischemia reperfusion injury of female rats via modulation of peroxisome proliferator activated receptor gamma and heme-oxygenase 1. Int Immunopharmacol. 2018; 62: 7-14.
  • 16. Shokoohi M, Soltani M, Abtahi-Eivary S-H, Niazi V, Poor M J R, Ravaei H, Salimnejad R, 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 Pacific Journal of Reproduction 2019; 8: 148-56.
  • 17. Malihe S, Maryam M, Hosein A, Majid S. The protective effect of Matricaria chamomilla extract on histological damage and oxidative stress induced by Torsion/Detorsion in adult rat ovary, International Journal Of Womens Health And Reproduction Sciences,2017; 5; 3,187-92.
  • 18. Şahin Ç, Yıldırm N, Hortu İ, Akdemir A, Özşener S, Yiğittürk G, Erbaş O. Tadalafil attenuates ischemic damage as well as reperfusion injury in the rat ovary. J Turk Ger Gynecol Assoc 2020; 21: 35-40
  • 19. Kumar S, Ashraf M. Tadalafil, a Phosphodiesterase Inhibitor Protects StemCells over Longer Period Against Hypoxia/Reoxygenation Injury Through STAT3/PKG-ISignaling. Stem Cells Dev. 2015; 24: 1332-41.
  • 20. Mojtaba A, Mohaddeseh S H, Maryam M, Majid S. Protective effect of tadalafil and verapamil on testicular function and oxidative stress after torsion/detorsion in adult male rat, Andrologia; 2018; 50; 8; e13068.
  • 21. Elmadbouh I, Ashraf M. Tadalafil, a long acting phosphodiesterase inhibitor, promotes bone marrow stem cell survival and their homing into ischemic myocardium for cardiac repair. Physiol Rep. 2017;5(21):e13480.
  • 22. Takeda A, Hayashi S, Teranishi Y, Imoto S, Nakamura H. Chronic adnexal torsion: An under-recognized disease entity. Eur J Obstet Gynecol Reprod Biol. 2017; 210: 45-53.
  • 23. Hortu I, Ozceltik G, Sahin C, Akman L, Yildirim N, Erbas O. GranulocyteColony-Stimulating Factor Prevents Ischemia/Reperfusion-Induced Ovarian Injury inRats: Evaluation of Histological and Biochemical Parameters. Reprod Sci. 2019; 26: 1389-94.

Tadalafil tedavisinin ratlarda over iskemi hasarına etkisi

Year 2021, Volume: 46 Issue: 1, 55 - 62, 31.03.2021

Abstract

Amaç: Her yaştan kadında en sık görülen jinekolojik cerrahi acil durumlarından biri olarak bilinen over iskemisi, yumurtalık perfüzyonunun bozulmasıdır. Sıçanlarda iskemi-reperfüzyon hasarı deneysel modelinde bir fosfodiesteraz-5 inhibitörü olan tadalafilin farklı doz ve tedavi süresinde over sağkalımı üzerindeki etkisini araştırmayı amaçladık.
Gereç ve Yöntem: Otuz dişi Wistar albino sıçan beş gruba ayrıldı. Yumurtalık iskemisi, tuba uterina adneksinin üç saat klemplenmesi ve bir saat reperfüze edilmesi suretiyle gerçekleştirildi. İlaç tedavileri şu şekilde verildi: Grup 1: salin (iskemik kontrol), Grup 2: tadalafil 1 mg / kg, Grup 3: tadalafil 10 mg / kg, Grup 4: tadalafil 1 mg / kg x 7 gün, Grup 5: tadalafil 10 mg / kg x 7 gün. Tedavilerin sonunda overleri çıkarıldı ve histopatolojik olarak değerlendirildi.
Bulgular: Grup 4 ve Grup 5'te, Grup 1'e kıyasla vasküler konjesyon, kanama, ödem ve nötrofilik infiltrasyon anlamlı derecede daha azdı. Tüm gruplar, Grup 1'e kıyasla nötrofilik infiltrasyonda anlamlı düşüş gösterdi. 7 günlük tadalafil tedavisinin iskemik kontrol grubu ile karşılaştırıldığında sıçanlardaki over doku hasarını belirgin derecede azalttığını tespit ettik.
Sonuç: Bu çalışmadaki sonuçlar overin iskemik hasarında tadalafil tedavisinin bu hasarını sınırlamada etkili olduğunu göstermiştir. Doku hasarı skorlarındaki azalma, tadalafil gibi PDE-5 inhibitörleri ile tedavinin konservatif olarak tedavi edilen overlerin iyileşmesine katkıda bulunabileceğini ve adneksiyal torsiyonun tedavisinde rol alabileceğini ortaya koymaktadır.

References

  • 1. Erturk N, Elbe H, Erdemli ME, Aktas S, Yigitturk G, Aksungur Z, Suzen A, et al. Protective effects of sildenafil and resveratrol on ovarian ischemiareperfusion injury in rats. Biomedical Research 2017; 28: 9113-20.
  • 2. Laganà AS, Sofo V, Salmeri FM, Palmara VI, Triolo O, Terzić MM, Patrelli TS, et al. Oxidative Stress during Ovarian Torsion in Pediatric and Adolescent Patients: Changing The Perspective of The Disease. Int J Fertil Steril. 2016; 9: 416-23.
  • 3. Isik A, Peker K, Gursul C, Sayar I, Firat D, Yilmaz I, Demiryilmaz I. The effect of ozone and naringin on intestinal ischemia/reperfusion injury in an experimental model, International Journal of Surgery. 2015; 21: 38e4439.
  • 4. Dasgupta R, Renaud E, Goldin AB, Baird R, Cameron DB, Arnold MA, DiefenbachKA, et al. Ovarian torsion inpediatric and adolescent patients: A systematic review. J Pediatr Surg. 2018; 53: 1387-91.
  • 5. Childress KJ, Dietrich JE. Pediatric Ovarian Torsion. Surg Clin North Am. 2017; 97: 209-21.
  • 6. Yildirim N, Simsek D, Kose S, Yildirim AGS, Guven C, Yigitturk G, Erbas O. The protective effect of Gingko biloba in a rat model of ovarian ischemia/reperfusion injury: Improvement in histological and biochemical parameters. Adv Clin Exp Med. 2018; 27: 591-7.
  • 7. Çılgın H, Şimşek M, Bal R. Can adnexal torsion be predicted by measuringplasma heat shock protein 70 level? An experimental study. Arch Gynecol Obstet.2017; 296: 941-6.
  • 8.Altintas Aykan D.,Yaman S. Tadalafil exerts a dual effect in behavioral pain responses in rats. Ann Med Res 2020; 27: 749-54.
  • 9. Wietzikoski EGG, Foiatto JC, Czeczko NG, Malafaia O, Koleski FC, Mierzwa TC, Gomes RPX. Tadalafil protector effect during ischemia-reperfusion in rats. Acta Cir Bras. 2017; 32: 973-83.
  • 10 . Gasanov F, Aytac B, Vuruskan H. The effects of tadalafil on renal ischemia reperfusion injury: an experimental study. Bosn J Basic Med Sci. 2011; 11: 158-62.
  • 11.Ural A, Bilgen F, Altıntaş Aykan D, Bahar AY, Bekerecioğlu M, Altıntaş Ural D. Effects of dabigatran and fondaparinux on degloving injuries: An experimental study. Ulus Travma Acil Cerrahi Derg 2020; 26: 343-50.
  • 12. Farnaz Shokri, Majid Shokoohi, Ayda Roudi Rasht Abadi, Hossein Kalarestaghi. The ameliorative effect of Galega officinalis extract on histological damages, oxidative stress induced by torsion-detorsion in adult rats’ ovarian, Int J Womens Health Reprod Sci. 2019; 7; 119-23.
  • 13. 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.
  • 14. Balasubramaniam D, Duraisamy KY, Ezhilmani M. Laparoscopic Detorsion andFertility Preservation in Twisted Ischemic Adnexa - A Single-Center Prospective Study. Gynecol Minim Invasive Ther. 2020; 9: 24-8.
  • 15. Refaie MMM, El-Hussieny M. Protective effect of pioglitazone on ovarian ischemia reperfusion injury of female rats via modulation of peroxisome proliferator activated receptor gamma and heme-oxygenase 1. Int Immunopharmacol. 2018; 62: 7-14.
  • 16. Shokoohi M, Soltani M, Abtahi-Eivary S-H, Niazi V, Poor M J R, Ravaei H, Salimnejad R, 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 Pacific Journal of Reproduction 2019; 8: 148-56.
  • 17. Malihe S, Maryam M, Hosein A, Majid S. The protective effect of Matricaria chamomilla extract on histological damage and oxidative stress induced by Torsion/Detorsion in adult rat ovary, International Journal Of Womens Health And Reproduction Sciences,2017; 5; 3,187-92.
  • 18. Şahin Ç, Yıldırm N, Hortu İ, Akdemir A, Özşener S, Yiğittürk G, Erbaş O. Tadalafil attenuates ischemic damage as well as reperfusion injury in the rat ovary. J Turk Ger Gynecol Assoc 2020; 21: 35-40
  • 19. Kumar S, Ashraf M. Tadalafil, a Phosphodiesterase Inhibitor Protects StemCells over Longer Period Against Hypoxia/Reoxygenation Injury Through STAT3/PKG-ISignaling. Stem Cells Dev. 2015; 24: 1332-41.
  • 20. Mojtaba A, Mohaddeseh S H, Maryam M, Majid S. Protective effect of tadalafil and verapamil on testicular function and oxidative stress after torsion/detorsion in adult male rat, Andrologia; 2018; 50; 8; e13068.
  • 21. Elmadbouh I, Ashraf M. Tadalafil, a long acting phosphodiesterase inhibitor, promotes bone marrow stem cell survival and their homing into ischemic myocardium for cardiac repair. Physiol Rep. 2017;5(21):e13480.
  • 22. Takeda A, Hayashi S, Teranishi Y, Imoto S, Nakamura H. Chronic adnexal torsion: An under-recognized disease entity. Eur J Obstet Gynecol Reprod Biol. 2017; 210: 45-53.
  • 23. Hortu I, Ozceltik G, Sahin C, Akman L, Yildirim N, Erbas O. GranulocyteColony-Stimulating Factor Prevents Ischemia/Reperfusion-Induced Ovarian Injury inRats: Evaluation of Histological and Biochemical Parameters. Reprod Sci. 2019; 26: 1389-94.
There are 23 citations in total.

Details

Primary Language English
Subjects Clinical Sciences (Other)
Journal Section Research
Authors

Dilan Altıntaş Ural 0000-0002-1976-9122

Duygun Altıntaş Aykan 0000-0001-8224-4006

Sezen Koçarslan 0000-0002-3512-1588

Adem Doğaner 0000-0002-0270-9350

Publication Date March 31, 2021
Acceptance Date October 1, 2020
Published in Issue Year 2021 Volume: 46 Issue: 1

Cite

MLA Altıntaş Ural, Dilan et al. “Effect of Tadalafil Treatment on Ovarian Ischemia Injury in Rats”. Cukurova Medical Journal, vol. 46, no. 1, 2021, pp. 55-62.