Background: Cyclophosphamide (CP) is a well-known alkylating anticancer agent used in the treatment of various malignant and non-malignant tumors. CP may also cause a variety of adverse effects, including reproductive toxicity. Amifostine is known as a cytoprotective drug having antioxidant properties. Objective: To evaluate the possible beneficial effects of amifostine on testicular toxicity induced by CP in rats. Materials and Methods: A total of 35 Sprague-Dawley rats were used in this experimental study. The CP group animals received a single dose of 200 mg/kg CP on Day 8 by intraperitoneal injection and were left untreated for the following seven days. The two remaining groups of animals were treated with 200 mg/kg/day amifostine (AMF 200) and 400 mg/kg/day amifostine (AMF 400) for seven days prior to and following a single intraperitoneal injection of CP. Morphometrical analysis and histological examination of testicular tissue were performed. Serum testosterone, luteinizing hormone, and follicle-stimulating hormone levels were measured in serum using commercial ELISA kits. The epidydimal sperm count was determined. Results: The tubular epithelial height in the testis was significantly higher in the AMF400 group compared to other groups (p < 0.001). Animals in the AMF400 group showed minimal debris in the tubules, no Sertoli cell damage, and the Johnsen scores were slightly higher in the AMF400 group. The epididymal sperm count was significantly lower in the CP-administered animals compared to the control animals and was significantly higher in the AMF200 and AMF400 groups compared to the CP group (p = 0.006, and p = 0.019 respectively). Conclusion: Amifostine, at a dose of 400 mg/kg, may have a protective effect on testicular damage induced by CP in rats.

Introduction: The protective and/or therapeutic potential of tadalafil (TDL) on cyclophosphamide (CP)-induced hemorrhagic cystitis (HC) and testicular dysfunction in rats was evaluated. Materials and Methods: 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. Results and Conclusion: 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.

Any polymorphism altering the function of klotho gene may result with stone formation. We found that there are more GG sequences of G395A gene in patients with UTSD. That may be a polymorphism of klotho gene which results with stone formation. Further studies with more patients should be accomplished which are combining the genetic and epigenetic factors associated with urolithiasis and klotho gene to enlighten the etiology of this disease.

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