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

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.

RESUMO OBJETIVOS: Examinamos os efeitos do tadalafil em um dos inibidores da fosfodiesterase tipo 5 (PDE5) em um modelo de rato com obstrução ureteral unilateral parcial e completa (UUO). MÉTODOS: Os ratos foram divididos em cinco grupos: sham (n = 6), obstrução ureteral unilateral parcial (PUUO, n = 6), PUUO com tadalafil (PUUO T; Cialis, 10 mg/72 h, intragástrica; Lilly, Indianapolis, Indiana, EUA), completa obstrução ureteral unilateral (CUUO, n = 6) e CUUO com tratamento com tadalafil (CUUO T). RESULTADOS: Quinze dias após a UUO, o ureter apresentou alterações nas camadas de urotélio e infiltração significativa de células inflamatórias nos grupos PUUO e CUUO. Em comparação com os grupos sham, PUUO e CUUO, houve um aumento grave da infiltração de células inflamatórias. O epitélio urotelial exibiu degeneração e perda celular devido às células epiteliais inchadas, atróficas e desnudas nos grupos PUUO e CUUO. Nos grupos PUUO T e CUUO T, o urotélio revelou menor degeneração e perda de células epiteliais. Nós mostramos que a expressão da actina do músculo liso-α (α-SMA) e do fator de crescimento transformador-β (TGF-β) foram exibidas como sub-regulação nos grupos PUUO e CUUO. A expressão do TGF-β foi diminuída positivamente correlacionada com a da α-SMA nos grupos de terapia com tadalafil, PUUO T e CUUO T. CONCLUSÃO: O tadalafil do inibidor da fosfodiesterase tipo 5 reduziu as expressões α-SMA e TGF-β nos ureteres obstruídos, medidos por exames bioquímicos. Além disso, o tadalafil diminuiu a degeneração do urotélio devido à diminuição da perda de células epiteliais e da infiltração de células inflamatórias. Nossos resultados mostram que o tadalafil previne ou retarda o início da inflamação do ureter e degeneração urotelial em ratos com UUO.

Early term effect of ureterorenoscopy (URS) on the Kidney: research measuring NGAL, KIM-1, FABP and CYS C levels in urine

ABSTRACT Aim: URS is a very commonly used procedure for treatment of ureter stones. Increased hydrostatic pressure in the collecting system linked to fluids used during the procedure may cause harmful effects on the kidney. The aim of this study is to determine whether the URS procedure has a negative effect on the kidney by investigating NGAL, KIM-1, FABP and Cys C levels in urine. Material and Methods: This study included 30 patients undergoing ureterorenoscopy (URS) for ureter stones. Urine samples were collected 5 times; before the URS procedure (control) and at 1, 3, 5 and 12 hours following the procedure. NGAL, KIM-1, FBAP and Cys C levels were measured in urine and compared with the control values. Results: The NGAL levels in urine before the procedure and at 1, 3, 5 and 12 hours after the procedure were 34.59±35.34; 62.72±142.32; 47.15±104.48; 45.23±163.16 and 44.99±60.79ng/mL, respectively (p=0.001). Similarly, the urinary KIM-1, FABP and Cys C levels were found to increase compared to control values; however this increase did not reach statistical significance (p >0.05). Conclusions: After the URS procedure, there were important changes in NGAL, FABP, KIM-1 and Cys C levels. These changes reached statistical significance for NGAL, but did not reach significance for the other parameters. In conclusion, the URS procedure significantly affects the kidney; however, this effect disappears over time.

The effect of tadalafil therapy on kidney damage caused by sepsis in a polymicrobial septic model induced in rats: a biochemical and histopathological study

ABSTRACT Introduction Sepsis is an inflammatory reaction to bacteria involving the whole body and is a significant cause of mortality and economic costs. The purpose of this research was to determine whether tadalafil exhibits a preventive effect on sepsis in a septic model induced in rats with cecal ligation and puncture (CLP). Materials and Methods Rats were randomly separated into groups, 10 rats in each: (i) a sham (control) group, (ii) an untreated sepsis group, (iii) a sepsis group treated with 5mg/kg tadalafil and (iv) a sepsis group treated with 10mg/kg tadalafil. A polymicrobial sepsis model was induced in rats using CLP. Rats were sacrificed after 16h, and blood and kidney tissues were collected for biochemical and histopathological study. Results Levels of the inflammatory parameter IL-6 decreased significantly in the sepsis groups receiving tadalafil in comparison with the untreated sepsis group (p<0.05). In terms of histopathology, inflammation scores investigated in kidney tissues decreased significantly in the sepsis groups receiving tadalafil compared to the untreated sepsis group (p<0.05). In addition, levels of creatinine and cystatin C measured in septic rats receiving tadalafil were lower by a clear degree than in septic rats (p<0.05). Conclusion In this study, tadalafil exhibited a preventive effect for sepsis-related damage by suppressing inflammation in serum and kidney tissue of septic rats in a polymicrobial sepsis model induced with CLP.