Effects of the chronic use of finasteride and doxazosin mesylate on the histomorphometric characteristics of the prostate: experimental study in rats
Tóm tắt
The objective of the present study is to evaluate the histomorphometric characteristics of the prostate of rats submitted to chronic (long-time) treatment with doxazosin mesylate, finasteride and both substances combined. Four groups of eight rats each were selected for this study and treated with saline solution (control), doxazosin mesylate, finasteride and combination of the drugs, during 10 months. After this time, the prostate was removed, weighed and sent for histological analysis. Prostate sections were stained with Masson trichrome. With an image analyzer, the percentage of smooth muscle, collagen, epithelium, acinar lumen and interstitial space was measured. Also, the minimum, medium and maximum epithelial thickness, number of acini per field, mean acinar area and the presence of papillary projections were evaluated. The mean prostate weight of rats treated with finasteride and combined treatment was lower when compared to the control group (P < 0.05). Prostate from rats treated with finasteride alone had a lower percentage of the epithelial component and a smaller minimum epithelial thickness than the control group (P < 0.05). The number of acini per field in the combined groups was higher than that observed in all other groups (P < 0.05). Also, rats of the finasteride and combined groups presented a reduced number of papillary projections when compared to the other groups (P < 0.05). Our study clearly showed the effects of finasteride on prostate tissue, and from a histomorphometric perspective, it was not able to detect any advantage of the combined treatment over the use of finasteride alone.
Tài liệu tham khảo
Chicharro-Molero JA, Burgos-Rodriguez R, Sanchez-Cruz JJ et al (1998) Prevalence of benign prostatic hyperplasia in Spanish men 40 years old or older. J Urol 159:878–882
Blom JH, Schroder FH (1992) Epidemiology and natural course of benign prostatic hyperplasia. Urologe A 31:129–134
Berry SJ, Coffey DS, Walsh PC et al (1984) The development of human benign prostatic hyperplasia with age. J Urol 132:474–479
Sagnier PP, MacFarlane G, Richard F et al (1994) Results of an epidemiological survey using a modified American Urological Association symptom index for benign prostatic hyperplasia in France. J Urol 151:1266–1270
McDonald H, Hux M, Brisson M et al (2004) An economic evaluation of doxazosin, finasteride and combination therapy in the treatment of benign prostatic hyperplasia. Can J Urol 11:2327–2340
McConnell JD, Roehrborn CG, Bautista OM et al (2003) The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia. N Engl J Med 349:2387–2398
Roehrborn CG, Siami P, Barkin J et al (2008) The effects of dutasteride, tamsulosin and combination therapy on lower urinary tract symptoms in men with benign prostatic hyperplasia and prostatic enlargement: 2-year results from the CombAT study. J Urol 179(2):616–621
Fitzpatrick JM, Kirby RS (2004) Two-drug therapy is best for symptomatic prostate enlargement: could a combination of doxazosin and finasteride change clinical practice? BJU Int 93:914–915
Kyprianou N (2003) Doxazosin and terazosin suppress prostate growth by inducing apoptosis: clinical significance. J Urol 169:1520–1525
Coffey DS, Walsh PC (1990) Clinical and experimental studies of benign prostatic hyperplasia. Urol Clin North Am 17:461–475
Dutkiewics S (2001) Efficacy and tolerability of drugs for treatment of benign prostatic hyperplasia. Int Urol Nephrol 32(3):423–432
Marks LS, Partin AW, Gormley GJ et al (1997) Prostate tissue composition and response to finasteride in men with symptomatic benign prostatic hyperplasia. J Urol 157:2171–2178
Bruskewitz R, Girman CJ, Fowler J et al (1999) Effect of finasteride on bother and other health-related quality of life aspects associated with benign prostatic hyperplasia. PLESS study group. Proscar long-term efficacy and safety study. Urology 54:670–678
Turkeri LN, Ozyurek M, Ersev D et al (2001) A Apoptotic regression of prostatic tissue induced by short-term doxazosin treatment in benign prostatic hyperplasia. Arch Esp Urol 54:191–196
Justulin LA Jr, Delella FK, Felisbino SL (2008) Doxazosin reduces cell proliferation and increases collagen fibers in rat prostatic lobes. Cell Tissue Res 332(1):171–183
Erdogru T, Ciftcioglu MA, Emreoglu I et al (2002) Apoptotic and proliferative index after Alpha-1-adrenoceptor antagonist and/or finasteride treatment in benign prostatic hyperplasia. Urol Int 69:287–292
Glassman DT, Chon JK, Borkowski A, Jacobs SC, Kyprianou N (2001) Combined effect of terazosin and finasteride on apoptosis, cell proliferation, and transforming growth factor-beta expression in benign prostatic hyperplasia. Prostate 46:45–51
Canda AE, Mungan MU, Yilmaz O et al (2006) Effects of finasteride on the vascular surface density, number of microvessels and vascular endothelial growth factor expression of the rat prostate. Int Urol Nephrol 38(2):275–280