A phosphodiesterase 5 inhibitor, tadalafil, suppresses stromal predominance and inflammation in a rat model of nonbacterial prostatitis

BMC Urol. 2019 Oct 23;19(1):99. doi: 10.1186/s12894-019-0525-x.

Abstract

Background: Chronic inflammation is thought to be a major causative factor for the development of benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS). Tadalafil, a phosphodiesterase type 5 inhibitor (PDE5-I), which has been used for the treatment of BPH-LUTS in daily practice, is known to act at several urinary organs. In this study, focused on the prostate, we examined the effect of tadalafil on the pathological changes and inflammatory factors in a rat nonbacterial prostatitis (NBP) model.

Methods: Forty ten-month-old male Wistar rats were divided into nonbacterial prostatitis (NBP), NBP with tadalafil treatment (NBP-tadalafil), control, and control treated with tadalafil (control-tadalafil) groups (n = 10 per group). The NBP and NBP-tadalafil groups were castrated and then received daily subcutaneous 17β-estradiol for 30 days. The control-tadalafil and NBP-tadalafil groups were administered daily oral tadalafil for 30 days. All rats were then sacrificed and pathological changes and inflammatory factors were assessed in the prostatic tissues.

Results: In the NBP group, the stroma-to-epithelium (S/E) ratio in the ventral prostate was significantly higher than in the control group (P < 0.001). In the NBP-tadalafil group, the S/E ratio was significantly lower than in the NBP group (P < 0.001). The macrophage levels and the extent of T-cell infiltration in the NBP-tadalafil group were significantly lower than in the NBP group (P < 0.005; P < 0.001, respectively). Compared with the NBP group, tissue concentrations of inflammatory cytokines, such as tumor necrosis factor-α, interleukin-8, and interleukin-1β, were significantly downregulated in the NBP-tadalafil group (P < 0.01; P < 0.05; P < 0.005, respectively).

Conclusions: Tadalafil suppressed stromal predominance and showed anti-inflammatory effects in a rat NBP model in association with downregulation of inflammatory cytokines.

Keywords: Benign prostatic hyperplasia; Inflammatory cytokines; Lower urinary tract symptoms; Nonbacterial prostatitis; Tadalafil.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Male
  • Phosphodiesterase 5 Inhibitors / pharmacology
  • Phosphodiesterase 5 Inhibitors / therapeutic use*
  • Prostate / drug effects
  • Prostate / pathology
  • Prostatitis / drug therapy*
  • Rats
  • Rats, Wistar
  • Tadalafil / pharmacology
  • Tadalafil / therapeutic use*

Substances

  • Phosphodiesterase 5 Inhibitors
  • Tadalafil