Positive outcomes of phosphodiesterase type 5 inhibitor on histopathologic and biochemical changes induced by ureteral obstruction

Abstract

SUMMARY OBJECTIVES: We examined the effects of tadalafil, one of the phosphodiesterase type 5 (PDE5) inhibitors, in a rat model of with partial and complete unilateral ureteral obstruction (UUO). METHODS: The rats were divided into 5 groups: sham (n=6), partial unilateral ureteral obstruction (PUUO, n=6), PUUO with tadalafil treatment (PUUO+T; Cialis, 10 mg/72 h, intragastric; Lilly, Indianapolis, Indiana, USA), complete unilateral ureteral obstruction (CUUO, n=6), and CUUO with tadalafil treatment (CUUO+T). RESULTS: Fifteen days after the UUO, the ureter presented changes in the layers of urothelium and significant infiltration of inflammatory cells in the PUUO and CUUO groups. Compared with the sham, PUUO and CUUO groups had severe increased inflammatory cell infiltration. The urothelial epithelium exhibited cell degeneration and loss because of the swollen, atrophic, and denuded epithelial cells in the PUUO and CUUO groups. In the PUUO+T and CUUO+T groups, the urothelium revealed less epithelial cell degeneration and loss. The expressions of α-smooth muscle actin (α-SMA) and transforming growth factor-β (TGF-β) exhibited up-regulation in the PUUO and CUUO groups. The expression of TGF-β decreased positively correlated with that of α-SMA in the tadalafil therapy groups, PUUO+T and CUUO+T. CONCLUSION: The phosphodiesterase type 5 inhibitor's tadalafil reduced expressions of α-SMA and TGF-β in the obstructed ureters, measured by biochemical examinations. In addition, tadalafil decreased urothelium degeneration due to the decreased epithelial cell loss and inflammatory cell infiltration. Our results show that tadalafil prevents or slows down the onset of ureter inflammation and urothelial degeneration in rats with UUO.

Current Concepts on the Reno-Protective Effects of Phosphodiesterase 5 Inhibitors in Acute Kidney Injury: Systematic Search and Review

“…The main characteristics and results of the human studies evaluating the potential reno-protective effects of PDE5Is are summarized in Table 1 [17,24,38,39]. The main characteristics and results of the animal studies on currently proposed AKI models evaluating the potential reno-protective effects of sildenafil, tadalafil, icariin, vardenafil, zaprinast-udenafil are summarized in Table 2 [23,30,, Table 3 [29,35,45,49,[62][63][64][65][66][67][68][69][70][71][72][73][74], Table 4 [18,75,76], Table 5 [45,77,78], and Table 6 [21,40,79,80], respectively. The main characteristics and results of the animal studies in the AKI-CKD transition spectrum (focusing on renal function and/or structure alterations for up to three months, not fulfilling the KDIGO definition for CKD [6]) evaluating the potential reno-protective effects of sildenafil, tadalafil, icariin, vardenafil, zaprinast-udenafil are summarized in Table A1 [109,110], respectively (Appendix B).…”

Advancements in Phosphodiesterase 5 Inhibitors: Unveiling Present and Future Perspectives

“…Most reported preclinical studies highlighted a promising potential of PDE5-Is to improve renal function and histopathological changes via collaborative mechanisms, including antioxidative, anti-inflammatory, anti-apoptotic, antifibrotic pathways along with suppression of DNA damage and improving renal blood flow, NOS levels, endothelial function and mitochondrial biogenesis. Most recently, tadalafil was also reported to avert the onset of ureter inflammation and urothelial degeneration in a unilateral ureteral obstruction animal model via modulation of various histopathologic and biochemical changes [ 183 ].…”