open access

Vol 90, No 9 (2019)
Research paper
Published online: 2019-09-30
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Comparison of the protective effects of sildenafil, vardenafil and tadalafil treatments in ischemia-reperfusion injury in rat ovary

Onder Sakin1, Ali Doğukan Anğın1, Emine Eda Akalın1, Muzaffer Seyhan Cikman1, Kayhan Basak, Asuman Orcun Kaptanagasi
·
Pubmed: 31588548
·
Ginekol Pol 2019;90(9):513-519.
Affiliations
  1. Kartal Dr Lutfi Kirdar Training and Research Hospital, Kartal, Istanbul, Turkey

open access

Vol 90, No 9 (2019)
ORIGINAL PAPERS Gynecology
Published online: 2019-09-30

Abstract

Objectives: The aim of this study was to compare the effects of sildenafil, vardenafil and tadalafil in treatment for ischemia/ reperfusion injury which is created experimentally in rat ovaries. 

Material and methods: For this study, 30 female Wistar albino rats were used, and the rats were separated randomly into five groups consisting of six rats each: normal, torsion-detorsion, torsion-detorsion + sildenafil 1.4 mg/kg, torsion-detorsion + vardenafil 1.7 mg/kg and torsion-detorsion + tadalafil 5.0 mg/kg. The agents were given intraperitoneally 30 minutes before detorsion. An ovarian torsion procedure was implemented in all other groups for 3 hours with the exception of the normal group. Then, a detorsion procedure was implemented to the groups for 3 hours. 

Results: The sildenafil and vardenafil treatments showed protective effect by preventing significant increase in inflammation parameters. (p = 0.058, 0.138). The tadalafil treatment was only protective for cellular degeneration (p = 0.140). The vardenafil treatment was protective for edema (p = 0.238), vascular congestion (p = 0.111), inflammation (p = 0.138) and cellular degeneration (p = 0.532). Sildenafil, vardenafil and tadalafil inhibited the increase of atretic follicle. AMH levels were statistically different between torsion and detorsion and vardenafil group (p = 0.004, 0.004), whereas tadalafil and sildenafil groups were similar to normal group (p = 0.108, 0.108).

Conclusions: PDE inhibitors were found to be effective in reducing ovarian ischemia/reperfusion injury. Sildenafil and tadalafil seem to be more effective than the vardenafil in protecting the ovarian reserve.

Abstract

Objectives: The aim of this study was to compare the effects of sildenafil, vardenafil and tadalafil in treatment for ischemia/ reperfusion injury which is created experimentally in rat ovaries. 

Material and methods: For this study, 30 female Wistar albino rats were used, and the rats were separated randomly into five groups consisting of six rats each: normal, torsion-detorsion, torsion-detorsion + sildenafil 1.4 mg/kg, torsion-detorsion + vardenafil 1.7 mg/kg and torsion-detorsion + tadalafil 5.0 mg/kg. The agents were given intraperitoneally 30 minutes before detorsion. An ovarian torsion procedure was implemented in all other groups for 3 hours with the exception of the normal group. Then, a detorsion procedure was implemented to the groups for 3 hours. 

Results: The sildenafil and vardenafil treatments showed protective effect by preventing significant increase in inflammation parameters. (p = 0.058, 0.138). The tadalafil treatment was only protective for cellular degeneration (p = 0.140). The vardenafil treatment was protective for edema (p = 0.238), vascular congestion (p = 0.111), inflammation (p = 0.138) and cellular degeneration (p = 0.532). Sildenafil, vardenafil and tadalafil inhibited the increase of atretic follicle. AMH levels were statistically different between torsion and detorsion and vardenafil group (p = 0.004, 0.004), whereas tadalafil and sildenafil groups were similar to normal group (p = 0.108, 0.108).

Conclusions: PDE inhibitors were found to be effective in reducing ovarian ischemia/reperfusion injury. Sildenafil and tadalafil seem to be more effective than the vardenafil in protecting the ovarian reserve.

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Keywords

adnexal torsion; ischemia-reperfusion injury; sildenafil; vardenafil; tadalafil; rat model

About this article
Title

Comparison of the protective effects of sildenafil, vardenafil and tadalafil treatments in ischemia-reperfusion injury in rat ovary

Journal

Ginekologia Polska

Issue

Vol 90, No 9 (2019)

Article type

Research paper

Pages

513-519

Published online

2019-09-30

Page views

1608

Article views/downloads

1235

DOI

10.5603/GP.2019.0089

Pubmed

31588548

Bibliographic record

Ginekol Pol 2019;90(9):513-519.

Keywords

adnexal torsion
ischemia-reperfusion injury
sildenafil
vardenafil
tadalafil
rat model

Authors

Onder Sakin
Ali Doğukan Anğın
Emine Eda Akalın
Muzaffer Seyhan Cikman
Kayhan Basak
Asuman Orcun Kaptanagasi

References (35)
  1. Aslan M, Erkanli Senturk G, Akkaya H, et al. The effect of oxytocin and Kisspeptin-10 in ovary and uterus of ischemia-reperfusion injured rats. Taiwan J Obstet Gynecol. 2017; 56(4): 456–462.
  2. Pınar N, Soylu Karapınar O, Özcan O, et al. Protective effects of tempol in an experimental ovarian ischemia-reperfusion injury model in female Wistar albino rats. Can J Physiol Pharmacol. 2017; 95(7): 861–865.
  3. Huang Ci, Hong MK, Ding DC. A review of ovary torsion. Ci Ji Yi Xue Za Zhi. 2017; 29(3): 143–147.
  4. Sintim-Damoa A, Majmudar AS, Cohen HL, et al. Pediatric Ovarian Torsion: Spectrum of Imaging Findings. Radiographics. 2017; 37(6): 1892–1908.
  5. Oktem O, Oktay K. Quantitative assessment of the impact of chemotherapy on ovarian follicle reserve and stromal function. Cancer. 2007; 110(10): 2222–2229.
  6. Yeral I, Sayan CD, Karaca G, et al. What is the protective effect of krill oil on rat ovary against ischemia-reperfusion injury? J Obstet Gynaecol Res. 2019; 45(3): 592–599.
  7. Behroozi-Lak T, Zarei L, Moloody-Tapeh M, et al. Protective effects of intraperitoneal administration of nimodipine on ischemia-reperfusion injury in ovaries: Histological and biochemical assessments in a rat model. J Pediatr Surg. 2017; 52(4): 602–608.
  8. Nayki C, Nayki U, et al. Keskin Cimen F, The effect of rutin on ovarian ischemia-reperfusion injury in a rat model. Gynecol Endocrinol. 2018; 34(9): 809–814.
  9. Tokgoz VY, Sipahi M, Keskin O, et al. Protective effects of vitamin D on ischemia-reperfusion injury of the ovary in a rat model. Iran J Basic Med Sci. 2018; 21(6): 593–599.
  10. Kolac UK, Ustuner MC, Tekin N, et al. The Anti-Inflammatory and Antioxidant Effects of Salvia officinalis on Lipopolysaccharide-Induced Inflammation in Rats. J Med Food. 2017; 20(12): 1193–1200.
  11. Centeno JM, Orti M, Salom JB, et al. Nitric oxide is involved in anoxic preconditioning neuroprotection in rat hippocampal slices. Brain Res. 1999; 836(1-2): 62–69.
  12. Kass DA, Takimoto E, Nagayama T, et al. Phosphodiesterase regulation of nitric oxide signaling. Cardiovasc Res. 2007; 75(2): 303–314.
  13. Celik M, Aksoy AN, Aksoy H, et al. Sildenafil reduces ischemia-reperfusion injury in rat ovary: biochemical and histopathological evaluation. Gynecol Obstet Invest. 2014; 78(3): 162–167.
  14. Beheshtian A, Salmasi AH, Payabvash S, et al. Protective effects of sildenafil administration on testicular torsion/detorsion damage in rats. World J Urol. 2008; 26(2): 197–202.
  15. Inan M, Uz YH, Kizilay G, et al. Protective effect of sildenafil on liver injury induced by intestinal ischemia/reperfusion. J Pediatr Surg. 2013; 48(8): 1707–1715.
  16. Shih PK, Cheng CM, Li HP, et al. Pretreatment with sildenafil alleviates early lung ischemia-reperfusion injury in a rat model. J Surg Res. 2013; 185(2): e77–e83.
  17. Choi DE, Jeong JY, Lim BJ, et al. Pretreatment of sildenafil attenuates ischemia-reperfusion renal injury in rats. Am J Physiol Renal Physiol. 2009; 297(2): F362–F370.
  18. Uzun H, Konukoglu D, Nuri MK, et al. The effects of sildenafil citrate on ischemic colonic anastomotic healing in rats: its relationship between nitric oxide and oxidative stress. World J Surg. 2008; 32(9): 2107–2113.
  19. BAŞ H, KARA Ö, KARA M, et al. Protective effect of vardenafil on ischemia–reperfusion injury in rat ovary. TURKISH JOURNAL OF MEDICAL SCIENCES. 2013; 43: 684–689.
  20. Parlakgumus HA, Aka Bolat F, Bulgan Kilicdag E, et al. Atorvastatin for ovarian torsion: effects on follicle counts, AMH, and VEGF expression. Eur J Obstet Gynecol Reprod Biol. 2014; 175: 186–190.
  21. Incebiyik A, Seker A, Camuzcuoglu H, et al. Does sildenafil have protective effects against ovarian ischemia-reperfusion injury in rats? Arch Gynecol Obstet. 2015; 291(6): 1283–1288.
  22. Yurtcu E, Togrul C, Ozyer S, et al. Dose dependent protective effects of vardenafil on ischemia-reperfusion injury with biochemical and histopathologic evaluation in rat ovary. J Pediatr Surg. 2015; 50(7): 1205–1209.
  23. Arikan DC, Bakan V, Kurutas EB, et al. Protective effect of tadalafil on ischemia/reperfusion injury of rat ovary. J Pediatr Surg. 2010; 45(11): 2203–2209.
  24. Porst H, Padma-Nathan H, Giuliano F, et al. Efficacy of tadalafil for the treatment of erectile dysfunction at 24 and 36 hours after dosing: a randomized controlled trial. Urology. 2003; 62(1): 121–125.
  25. Hopps CV, Mulhall JP. Novel agents for sexual dysfunction. BJU Int. 2003; 92(6): 534–538.
  26. Daugan A, Grondin P, Ruault C, et al. The discovery of tadalafil: a novel and highly selective PDE5 inhibitor. 2: 2,3,6,7,12,12a-hexahydropyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4-dione analogues. J Med Chem. 2003; 46(21): 4533–4542.
  27. Mehrotra N, Gupta M, Kovar A, et al. The role of pharmacokinetics and pharmacodynamics in phosphodiesterase-5 inhibitor therapy. Int J Impot Res. 2007; 19(3): 253–264.
  28. Calis P, Bozdag G, Karakoc Sokmensuer L, et al. Does ischemia-reperfusion injury affect ovarian reserve and follicle viability in a rat model with adnexal torsion? Eur J Obstet Gynecol Reprod Biol. 2015; 185: 126–130.
  29. Dewailly D, Andersen CY, Balen A, et al. The physiology and clinical utility of anti-Mullerian hormone in women. Hum Reprod Update. 2014; 20(3): 370–385.
  30. Riggs RM, Duran EH, Baker MW, et al. Assessment of ovarian reserve with anti-Müllerian hormone: a comparison of the predictive value of anti-Müllerian hormone, follicle-stimulating hormone, inhibin B, and age. Am J Obstet Gynecol. 2008; 199(2): 202.e1–202.e8.
  31. Kaya C, Turgut H, Cengiz H, et al. Effect of detorsion alone and in combination with enoxaparin therapy on ovarian reserve and serum antimüllerian hormone levels in a rat ovarian torsion model. Fertil Steril. 2014; 102(3): 878–884.e1.
  32. Visser JA, Durlinger ALL, Peters IJJ, et al. Regulation of ovarian function: the role of anti-Müllerian hormone. Reproduction. 2002; 124(5): 601–609.
  33. Baarends WM, Uilenbroek JT, Kramer P, et al. Anti-müllerian hormone and anti-müllerian hormone type II receptor messenger ribonucleic acid expression in rat ovaries during postnatal development, the estrous cycle, and gonadotropin-induced follicle growth. Endocrinology. 1995; 136(11): 4951–4962.
  34. Ozler A, Turgut A, Görük NY, et al. Evaluation of the protective effects of CoQ₁₀ on ovarian I/R injury: an experimental study. Gynecol Obstet Invest. 2013; 76(2): 100–106.
  35. Sahin Ersoy G, Eken M, Tal R, et al. N-acetylcysteine leads to greater ovarian protection than enoxaparin sodium in a rat ovarian torsion model. Reprod Biomed Online. 2016; 33(1): 93–101.

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