Comparison of the protective effects of sildenafil, vardenafil and tadalafil treatments in ischemia-reperfusion injury in rat ovary
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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.
Keywords: adnexal torsionischemia-reperfusion injurysildenafilvardenafiltadalafilrat model
References
- 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.
- 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.
- Huang Ci, Hong MK, Ding DC. A review of ovary torsion. Ci Ji Yi Xue Za Zhi. 2017; 29(3): 143–147.
- Sintim-Damoa A, Majmudar AS, Cohen HL, et al. Pediatric Ovarian Torsion: Spectrum of Imaging Findings. Radiographics. 2017; 37(6): 1892–1908.
- Oktem O, Oktay K. Quantitative assessment of the impact of chemotherapy on ovarian follicle reserve and stromal function. Cancer. 2007; 110(10): 2222–2229.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Kass DA, Takimoto E, Nagayama T, et al. Phosphodiesterase regulation of nitric oxide signaling. Cardiovasc Res. 2007; 75(2): 303–314.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Hopps CV, Mulhall JP. Novel agents for sexual dysfunction. BJU Int. 2003; 92(6): 534–538.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Visser JA, Durlinger ALL, Peters IJJ, et al. Regulation of ovarian function: the role of anti-Müllerian hormone. Reproduction. 2002; 124(5): 601–609.
- 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.
- 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.
- 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.
