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Comparison of the effects of pentoxifylline, simvastatin, tamoxifen, and losartan on cavernous bodies after penile fracture in rats: a stereological study

International Journal of Impotence Research volume 32, pages 338–344 (2020)Cite this article

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Abstract

Penile fracture (PF) is described as a rupture and fibrosis of the cavernous bodies. This study aimed to collect quantitative data on the impacts of pentoxifylline, simvastatin, tamoxifen, and losartan on cavernous body structure after PF. The rats were divided into six groups. The control group received anesthesia and incision without actual PF. The other groups (second to sixth) underwent PF induction in addition to administration of distilled water, pentoxifylline (200 mg/kg/day), simvastatin (40 mg/kg/day), tamoxifen (10 mg/kg/day), and losartan (20 mg/kg/day) for 8 weeks. The volumes of cavernous bodies, collagen bundles, and vessels and number of fibroblasts were increased significantly in the PF group in comparison to the control rats (p < 0.01), indicating a fibrotic process. Moreover, the mean volume of the cavernous bodies decreased in the groups with PF that received pentoxifylline, simvastatin, tamoxifen, or losartan when compared with the PF group. However, the volumes of the collagen bundles and vessels as well as the population of fibroblasts remained at the control level or even lower in PF plus pentoxifylline, simvastatin, tamoxifen, and losartan groups. This indicated the anti-fibrotic effects of the four drugs. It can be concluded that pentoxifylline, simvastatin, tamoxifen, and losartan could reduce fibrosis activities by minimizing the formation of collagen bundles and vessels as well as decreasing the population of fibroblasts 8 weeks after PF. Yet, losartan brought about a better outcome compared with the other chemicals.

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References

  1. Cho MC, Song WH, Paick JS. Suppression of cavernosal fibrosis in a rat model. Sex Med Rev. 2018;6:572–82. https://doi.org/10.1016/j.sxmr.2018.02.007.

    Article  PubMed  Google Scholar 

  2. Gonzalez-Cadavid NF. Mechanisms of penile fibrosis. J Sex Med. 2009;6(Suppl 3):353–62. https://doi.org/10.1111/j.1743-6109.2008.01195.x

    Article  PubMed  Google Scholar 

  3. Akgül T, Ayyildiz A, Cebeci O, Nuhoğlu B, Ozer E, Germiyanoğlu C, et al. Effect of cyanoacrylic glue on penile fracture: an experimental study. J Urol. 2008;180:749–52. https://doi.org/10.1016/j.juro.2008.03.181.

    Article  PubMed  Google Scholar 

  4. Blair BM, Vilson F, Kocher NJ, Kloniecke E, Clark JY. Longitudinal rupture of distal corpus cavernosum with concomitant urethral injury: an uncommon result of a common mechanism. Urology 2018;118:e5–6. https://doi.org/10.1016/j.urology.2018.01.008.

    Article  PubMed  Google Scholar 

  5. de Carvalho AM Jr, de Melo FM, Félix GA, Sarmento JF, Capriglione ML. Penile fracture with urethral trauma. Rev Col Bras Cir. 2013;40:351–3.

    Article  Google Scholar 

  6. El-Taher AM, Aboul-Ella HA, Sayed MA, Gaafar AA. Management of penile fracture. J Trauma. 2004;56:1138–40.

    Article  Google Scholar 

  7. Velnar T, Bailey T, Smrkolj V. The wound healing process: an overview of the cellular and molecular mechanisms. J Int Med Res. 2009;37:1528–42.

    Article  CAS  Google Scholar 

  8. Albersen M, Fandel TM, Zhang H, Banie L, Lin G, De Ridder D, et al. Pentoxifylline promotes recovery of erectile function in a rat model of post prostatectomy erectile dysfunction. Eur Urol. 2011;59:286–96. https://doi.org/10.1016/j.eururo.2010.10.034.

    Article  CAS  PubMed  Google Scholar 

  9. Ahmadi M, Khalili H. Potential benefits of pentoxifylline on wound healing. Expert Rev Clin Pharmacol. 2016;9:129–42. https://doi.org/10.1586/17512433.2016.1109443.

    Article  CAS  PubMed  Google Scholar 

  10. Rego AC, Araújo Filho I, Damasceno BP, Egito ES, Silveira IA, Brandão-Neto J, et al. Simvastatin improves the healing of infected skin wounds of rats. Acta Cir Bras. 2007;22(Suppl 1):57–63.

    Article  Google Scholar 

  11. Mehrvarz S, Ebrahimi A, Sahraei H, Bagheri MH, Fazili S, Manoochehry S, et al. Effects of topical tamoxifen on wound healing of burned skin in rats. Arch Plast Surg. 2017;44:378–83.

    Article  Google Scholar 

  12. Criss CN, Gao Y, De Silva G, Yang J, Anderson JM, Novitsky YW, et al. The effects of Losartan on abdominal wall fascial healing. Hernia. 2015;19:645–50. https://doi.org/10.1007/s10029-014-1241-9.

  13. Mun JH, Kim YM, Kim BS, Kim JH, Kim MB, Ko HC. Simvastatin inhibits transforming growth factor-β1-induced expression of type I collagen, CTGF, and α-SMA in keloid fibroblasts. Wound Repair Regen. 2014;22:125–33. https://doi.org/10.1111/wrr.12136.

    Article  PubMed  Google Scholar 

  14. Kim D, Lee AS, Jung YJ, Yang KH, Lee S, Park SK, et al. Tamoxifen ameliorates renal tubulointerstitial fibrosis by modulation of estrogen receptor α-mediated transforming growth factor-β1/Smad signaling pathway. Nephrol Dial Transpl. 2014;29:2043–53. https://doi.org/10.1093/ndt/gfu240.

    Article  CAS  Google Scholar 

  15. Molina-Molina M, Serrano-Mollar A, Bulbena O, Fernandez-Zabalegui L, Closa D, Marin-Arguedas A, et al. Losartan attenuates bleomycin induced lung fibrosis by increasing prostaglandin E2 synthesis. Thorax. 2006;61:604–10.

    Article  CAS  Google Scholar 

  16. Mohamed DI, Elmelegy AA, El-Aziz LF, Abdel Kawy HS, AbdEl-Samad AA, El-Kharashi OA. Hepatoprotective effects of early pentoxifylline administration on hepatic injury induced by concanavalin A in rat. Can J Physiol Pharmacol. 2014;92:490–7. https://doi.org/10.1139/cjpp-2014-0085.

    Article  CAS  PubMed  Google Scholar 

  17. Xiao X, Chang G, Liu J, Sun G, Liu L, Qin S, et al. Simvastatin ameliorates ventricular remodeling via the TGF-β1 signaling pathway in rats following myocardial infarction. Mol Med Rep. 2016;13:5093–101. https://doi.org/10.3892/mmr.2016.5178.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Karaca T, Yoldas O, Bilgin BC, Yilmaz OH, Karaca N, Simsek GG, et al. Does tamoxifen citrate prevent pulmonary fibrosis due to silica inhalation? Bratisl Lek Listy. 2015;116:440–5.

    CAS  PubMed  Google Scholar 

  19. Firoozmand LT, Sanches A, Damaceno-Rodrigues NR, Perez JD, Aragão DS, Rosa RM, et al. Blockade of AT1 type receptors for angiotensin II prevents cardiac microvascular fibrosisinduced by chronic stress in Sprague-Dawley rats. Stress. 2018;20:1–10. https://doi.org/10.1080/10253890.2018.1462328.

    Article  Google Scholar 

  20. Shirazi M, Noorafshan A, Serhan A. Effects of different suture materials used for the repair of hypospadias: a stereological study in a rat model. Urol Int. 2012;89:395–401. https://doi.org/10.1159/000343423.

    Article  PubMed  Google Scholar 

  21. Brown DL. Practical stereology applications for the pathologist. Vet Pathol. 2017;54:358–68. https://doi.org/10.1177/0300985817695781.

    Article  PubMed  Google Scholar 

  22. Khoshvakhti H, Yurt KK, Altunkaynak BZ, Türkmen AP, Elibol E, Aydın I, et al. Effects of melatonin on diclofenac sodium treated rat kidney: a stereological and histopathological study. Ren Fail. 2015;37:1379–83. https://doi.org/10.3109/0886022X.2015.1073556.

    Article  CAS  Google Scholar 

  23. Costa WS, Rebello SB, Cardoso LE, Cavalcanti AG, Sampaio FJ. Stereological and biochemical analysis of muscular and connective tissue components in the penile corpus cavernosum adjacent to the fibrous plaque of Peyronie’s disease. BJU Int. 2009;103:212–6. https://doi.org/10.1111/j.1464-410X.2008.08023.x.

    Article  Google Scholar 

  24. Ferreira FT, Dambros M, Bisogni S, Dambros MC, Scolfaro MR, Palma PC. Effects of testosterone supplementation on prevention of age-related penile remodeling. Aging Male. 2014;17:12–7. https://doi.org/10.3109/13685538.2013.873784.

    Article  CAS  PubMed  Google Scholar 

  25. Deniz ÖG, Altun G, Kaplan AA, Yurt KK, von Bartheld CS, Kaplan S. A concise review of optical, physical and isotropic fractionator techniques in neuroscience studies, including recent developments. J Neurosci Methods. 2018;310:45–53. https://doi.org/10.1016/j.jneumeth.2018.07.012.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Yurt KK, Kivrak EG, Altun G, Mohamed H, Ali F, Gasmalla HE, et al. A brief update on physical and optical disector applications and sectioning-staining methods in neuroscience. J Chem Neuroanat. 2018;93:16–29. https://doi.org/10.1016/j.jchemneu.2018.02.009.

    Article  PubMed  Google Scholar 

  27. Babaei S, Bayat M. Pentoxifylline accelerates wound healing process by modulating gene expression of MMP-1, MMP-3, and TIMP-1 in normoglycemic rats. J Investig Surg. 2015;28:196–201. https://doi.org/10.3109/08941939.2014.1002642.

    Article  Google Scholar 

  28. Bitto A, Minutoli L, Altavilla D, Polito F, Fiumara T, Marini H, et al. Simvastatin enhances VEGF production and ameliorates impaired wound healing in experimental diabetes. Pharm Res. 2008;57:159–69. https://doi.org/10.1016/j.phrs.2008.01.005.

    Article  CAS  Google Scholar 

  29. Khoshneviszadeh M, Ashkani-Esfahani S, Namazi MR, Noorafshan A, Geramizadeh B, Miri R. Topical simvastatin enhances tissue regeneration in full-thickness skin wounds in rat models. Iran J Pharm Res. 2014;13:263–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Yasasvini S, Anusa RS, VedhaHari BN, Prabhu PC, RamyaDevi D. Topical hydrogel matrix loaded with Simvastatin microparticles for enhanced wound healing activity. Mater Sci Eng C Mater Biol Appl. 2017;72:160–7. https://doi.org/10.1016/j.msec.2016.11.038.

    Article  CAS  PubMed  Google Scholar 

  31. Gragnani A, Warde M, Furtado F, Ferreira LM. Topical tamoxifen therapy in hypertrophic scars or keloids in burns. Arch Dermatol Res. 2010;302:1–4. https://doi.org/10.1007/s00403-009-0983-1.

    Article  CAS  PubMed  Google Scholar 

  32. Toblli JE, Stella I, Mazza ON, Ferder L, Inserra F. Different effect of losartan and amlodipine on penile structures in male spontaneously hypertensive rats. Am J Nephrol. 2004;24:614–23.

    Article  CAS  Google Scholar 

  33. Canguven O, Lagoda G, Sezen SF, Burnett AL. Losartan preserves erectile function after bilateral cavernous nerve injury via antifibrotic mechanisms in male rats. J Urol. 2009;181:2816–22. https://doi.org/10.1016/j.juro.2009.01.097.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The work was performed at the Histomorphometry and Stereology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. This article was a part of the thesis written by OK for the Specialty Degree in Urology awarded by Shiraz University of Medical Sciences. Hereby, the authors would like to thank Ms A. Keivanshekouh at the Research Improvement Center of Shiraz University of Medical Sciences for improving the use of English in the manuscript.

Funding

The study was financed by grant no. 94-01-01-10921 from Shiraz University of Medical Sciences, Shiraz, Iran.

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Authors and Affiliations

  1. Department of Urology, Shiraz University of Medical Sciences, Shiraz, Iran

    Ali Eslahi, Mehdi Shirazi & Omid Khoshnood

  2. Histomorphometry and Stereology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

    Mehdi Shirazi, Ali Noorafshan & Saied Karbalay-Doust

  3. Anatomy Department, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

    Ali Noorafshan & Saied Karbalay-Doust

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  1. Ali Eslahi
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Correspondence to Saied Karbalay-Doust.

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Eslahi, A., Shirazi, M., Khoshnood, O. et al. Comparison of the effects of pentoxifylline, simvastatin, tamoxifen, and losartan on cavernous bodies after penile fracture in rats: a stereological study. Int J Impot Res 32, 338–344 (2020). https://doi.org/10.1038/s41443-019-0175-2

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