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Anti-fibrotic effect of mycophenolate mofetil on Peyronie’s disease experimentally induced with TGF-β

International Journal of Impotence Research volume 32, pages 201–206 (2020)Cite this article

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Abstract

The aim of the present study was to evaluate the histological, histochemical, and stereological changes caused by mycophenolate mofetil (MMF) on the tunica albuginea of rat penises submitted to an injection of transforming growth factor beta (TGF-β) for the induction of Peyronie’s disease (PD). Twenty adult male Wistar rats were divided into four groups: Control group; TGF-β group (TGF-β injection); MMF-7d group (treated with MMF 7 days after induction with TGF-β); and MMF-30d group (treated with MMF 30 days after induction with TGF-β). The steorological evaluation included the relative volume of different types of connective fibres of the tunica albuginea. The histochemical analysis revealed the fragmentation and degradation of elastin in the tunica albuginea. This process was partially reversed in the MMF-7d group and a situation very close to normality was observed in the MMF-30d group. In the collagen III/collagen I ratio it was observed increase in this ratio in the TGF-β (59.4 ± 5.53) and MMF-7d (49 ± 18.2) groups and a decrease in the MMF-30d group (28.7 ± 4), approaching normality. The injection of TGF-β promoted fibrotic alterations in the penile tunica albuginea in Wistar rats corresponding to PD. In this model, MMF acts as a regenerating anti-fibrotic agent.

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References

  1. Joice GA, Burnett AL. Nonsurgical interventions for Peyronie’s disease: update as of 2016. World J Mens Health. 2016;34:65–72.

    Article  Google Scholar 

  2. Talib RA, Ibrahim MA, Cangüven Ö. Nonsurgical treatment options in Peyronie’s Disease: 2016 update. Turk J Urol. 2016;42:217–23.

    Article  Google Scholar 

  3. Al-Thakafi S, Al-Hathal N. Peyronie’s disease: a literature review on epidemiology, genetics, pathophysiology, diagnosis and work-up. Transl Androl Urol. 2016;5:280–9.

    Article  Google Scholar 

  4. Tal R, Heck M, Teloken P, Siegrist T, Nelson CJ, Mulhall JP. Peyronie’s disease following radical prostatectomy: incidence and predictors. J Sex Med. 2010;7:1254–61.

    Article  Google Scholar 

  5. Antoniassi TS, Spessoto LCF, Gonçalves Filho JR, Cavalcante VMM, da Silva EA, Facio MFW, et al. Risk factors for Peyronie’s disease in patients submitted to the Nesbit procedure. Int J Sci. 2016;5:131–3.

    Google Scholar 

  6. Bilgutay AN, Pastuszak AW. Peyronie’s disease: a review of etiology, diagnosis and management. Curr Sex Health Rep. 2015;7:117–31.

    Article  Google Scholar 

  7. Gonzalez-Cadavid NF, Rajfer J. Mechanisms of disease: new insights into the cellular and molecular pathology of Peyronie’s disease. Nat Clin Pract Urol. 2005;2:291–7.

    Article  CAS  Google Scholar 

  8. Gonzalez-Cadavid NF, Rajfer J. Experimental models of Peyronie’s disease. Implications for new therapies. J Sex Med. 2009;6:303–13.

    Article  CAS  Google Scholar 

  9. El-Sakka AI, Hassoba HM, Chui RM, Bhatnagar RS, Dahiya R, Lue TF. An animal model of Peyronie’s-like condition associated with an increase of transforming growth factor beta mRNA and protein expression. J Urol. 1997;158:2284–90.

    Article  CAS  Google Scholar 

  10. Somers KD, Sismour EN, Wright GL Jr, Devine CJ Jr, Gilbert DA, Horton CE. Isolation and characterization of collagen in Peyronie’s Disease. J Urol. 1989;141:629–31.

    Article  CAS  Google Scholar 

  11. Luangkhot R, Rutchik S, Agarwal V, Puglia K, Bhargava G, Melman A. Collagen alterations in the corpus cavernosum of men with sexual dysfunction. J Urol. 1992;148:467–71.

    Article  CAS  Google Scholar 

  12. Hellstrom WJ, Bivalacqua TJ. Peyronie’s disease: etiology, medical, and surgical therapy. J Androl. 2000;21:347–54.

    CAS  PubMed  Google Scholar 

  13. Castiglione F, Hedlund P, Van der Aa F, Bivalacqua TJ, Rigatti P, Van Poppel H, et al. Intratunical injection of human adipose tissue-derived stem cells prevents fibrosis and is associated with improved erectile function in a rat model of Peyronie’s disease. Eur Urol. 2013;63:551–60.

    Article  CAS  Google Scholar 

  14. Roos N, Poulalhon N, Farge D, Madelaine I, Mauviel A, Verrecchia F. In vitro evidence for a direct antifibrotic role of the immunosuppressive drug mycophenolate mofetil. J Pharm Exp Ther. 2007;321:583–9.

    Article  CAS  Google Scholar 

  15. Scheel PJ Jr, Piccini J, Rahman MH, Lawler LJ. Combined prednisone and mycophenolate mofetil treatment for retroperitoneal fibrosis. J Urol. 2007;178:140–3.

    Article  CAS  Google Scholar 

  16. Scheel PJ Jr, Sozio SM, Feeley N. Medical management of retroperitoneal fibrosis. Trans Am Clin Clim Assoc. 2012;123:283–90.

    Google Scholar 

  17. Hussein AA, Alwall A, Lue TF. All about Peyronie’s disease. Asian J Urol. 2015;2:70–8.

    Article  Google Scholar 

  18. El-Sakka AI, Hassan MU, Nunes L, Bhatnagar RS, Yen TS, Lue TF. Histological and ultrastructural alterations in an animal model of Peyronie’s disease. Br J Urol. 1998;81:445–52.

    Article  CAS  Google Scholar 

  19. Tzouvelekis A, Bouros E, Oikonomou A, Ntolios P, Zacharis G, Kolios G, et al. Effect and safety of mycophenolate mofetil in idiopathic pulmonary fibrosis. Pulm Med. 2011;2011:849035.

    Article  Google Scholar 

  20. American Veterinary Medical Association. Guideline for the Euthanasia of animals: ed. 2013; p.48. https://www.avma.org/KB/Policies/Documents/euthanasia.pdf.

  21. Behmer AO, Tolosa EMC, Neto AGF. Manual de práticas para histologia normal e patológica. São Paulo: EDART-EDUSP; 1976. p. 329.

  22. de Carvalho HF, Taboga SR. Fluorescence and confocal laser scanning microscopy imaging of elastic fibers in hematoxylin-eosin stained sections. Histochem Cell Biol. 1996;106:587–92.

    Article  Google Scholar 

  23. Weibel ER. Principles and methods for the morphometric study of the lung and other organs. Lab Invest. 1978;12:131–55.

    Google Scholar 

  24. Bilgutay AN, Pastuszak AW. Peyronie’s disease: what’s around the bend? Indian J Urol. 2016;32:6–14.

    Article  Google Scholar 

  25. Gokce A, Abd Elmageed ZY, Lasker GF, Bouljihad M, Kim H, Trost LW, et al. Adipose tissue-derived stem cell therapy for prevention and treatment of erectile dysfunction in a rat model of Peyronie’s disease. Andrology. 2014;2:244–51.

    Article  CAS  Google Scholar 

  26. Levine LA, Larsen SM. Surgery for Peyronie’s disease. Asian J Androl. 2013;15:27–34.

    Article  Google Scholar 

  27. Hellstrom WJG, Tan RBW, Liu G. Safety profile of collagenase Clostridium histolyticum stratified by degree of penile curvature in patients with Peyronie’s disease. Urology. 2017;S0090-4295:30477–6.

    Google Scholar 

  28. Gelbard M, Goldstein I, Hellstrom WJ, McMahon CG, Smith T, Tursi J, et al. Clinical efficacy, safety and tolerability of collagenase Clostridium histolyticum for the treatment of Peyronie disease in 2 large double-blind, randomized, placebo controlled phase 3 studies. J Urol. 2013;190:199–207.

    Article  CAS  Google Scholar 

  29. Yan S, Yap T, Minhas S. Collagenase clostridium histolyticum intralesional injections for the treatment of Peyronie’s disease: a safety profile. Transl Androl Urol. 2017;6:123–6.

    Article  Google Scholar 

Download references

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Authors and Affiliations

  1. Department of Urology, São José Rio Preto School of Medicine (FAMERP), São Paulo, Brazil

    Thiago Antoniassi, Fernando Nestor Fácio Júnior & Luís Cesar Fava Spessoto

  2. Department of Biology, São Paulo State University (UNESP /IBILCE), São Paulo, Brazil

    Luiz Henrique Guerra, Silvana Spegorin Campos & Sebastião Taboga

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  1. Thiago Antoniassi
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  2. Fernando Nestor Fácio Júnior
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  3. Luís Cesar Fava Spessoto
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  4. Luiz Henrique Guerra
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  6. Sebastião Taboga
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Correspondence to Fernando Nestor Fácio Júnior.

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Antoniassi, T., Júnior, F.N.F., Spessoto, L.C.F. et al. Anti-fibrotic effect of mycophenolate mofetil on Peyronie’s disease experimentally induced with TGF-β. Int J Impot Res 32, 201–206 (2020). https://doi.org/10.1038/s41443-019-0138-7

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