Yigitaslan Semra, Ozatik Orhan, Ozatik Fikriye Yasemin, Erol Kevser, Sirmagul Basar, Baseskioglu Ali Barbaros
Department of Pharmacology, School of Medicine, Eskisehir Osmangazi University, Eskisehir, Turkey.
Urol Int. 2014;93(1):55-62. doi: 10.1159/000352095. Epub 2013 Sep 18.
The protective and/or therapeutic potential of tadalafil (TDL) on cyclophosphamide (CP)-induced hemorrhagic cystitis (HC) and testicular dysfunction in rats was evaluated.
The animals except from the control group were divided into four groups and treated with saline, or 1, 5 or 10 mg/kg TDL orally (CP, TDL1, TDL5 and TDL10 groups, respectively) before and after CP injection. Body and organ weights, sperm count, cGMP, nitric oxide (NO), IL-6 and IL-10 levels in serum and bladder tissue, and serum testosterone (T), LH and FSH levels were determined. The histological analysis of bladder and testis was performed and the number of apoptotic cells was determined.
The CP group had decreased cGMP and NO levels in the bladder, serum T level (p < 0.05) and sperm count (p < 0.001) and higher IL-6 levels in serum and bladder (p < 0.01). Treatment with TDL resulted in increased cGMP (p < 0.001), NO (p < 0.05) and serum T (p < 0.05) levels. Histological analysis of the CP group showed severe HC in bladder and testicular damage. TDL-treated animals showed a dose-dependent improvement in all of these histological impairments. In conclusion, a selective inhibitor of phosphodiesterase-5 enzyme, TDL, showed a protective and/or therapeutic effect on CP-induced HC and testicular dysfunction in rats.
评估了他达拉非(TDL)对环磷酰胺(CP)诱导的大鼠出血性膀胱炎(HC)和睾丸功能障碍的保护和/或治疗潜力。
除对照组外,将动物分为四组,在CP注射前后分别口服生理盐水、或1、5或10mg/kg TDL(分别为CP、TDL1、TDL5和TDL10组)。测定体重和器官重量、精子计数、血清和膀胱组织中的cGMP、一氧化氮(NO)、白细胞介素-6和白细胞介素-10水平,以及血清睾酮(T)、促黄体生成素(LH)和促卵泡生成素(FSH)水平。对膀胱和睾丸进行组织学分析,并测定凋亡细胞数量。
CP组膀胱中cGMP和NO水平降低,血清T水平(p<0.05)和精子计数(p<0.001)降低,血清和膀胱中白细胞介素-6水平升高(p<0.01)。TDL治疗导致cGMP(p<0.001)、NO(p<0.05)和血清T(p<0.05)水平升高。CP组的组织学分析显示膀胱严重HC和睾丸损伤。TDL治疗的动物在所有这些组织学损伤方面均表现出剂量依赖性改善。总之,磷酸二酯酶-5酶的选择性抑制剂TDL对CP诱导的大鼠HC和睾丸功能障碍具有保护和/或治疗作用。