Protective and therapeutic effect of hydrogen sulfide on hemorrhagic cystitis and testis dysfunction induced with cyclophosphamide

Authors: FİKRİYE YASEMİN ÖZATİK, ORHAN ÖZATİK, YASEMİN TEKŞEN, SEMRA YİĞİTASLAN, NEZİHA SENEM ARI

Abstract: Backround/aim: Cyclophosphamide (CP) is a drug used for treatment of many malignant diseases. However, it can cause serious side effects such as hemorrhagic cystitis and male infertility. Hydrogen sulfide (H2 S) is a gaseous mediator and is suggested to have antioxidant, antiinflammatory, and antiapoptotic effects. In this study, dose-dependent effects of H2 S donor sodium hydrosulfide (NaHS) on cyclophosphamide-induced hemorrhagic cystitis and testicular dysfunction were investigated in rats. Material and methods: Rats were divided into 5 groups (n = 8): control, CP, NaHS25 μmol/kg, NaHS50 μmol/kg, and NaHS100 μmol/ kg. After treatment for 7 days intraperitoneally (ip), a single ip dose of CP 200 mg/kg was given on the 8th day. Then, treatment was continued for 7 days. In bladder and testicular tissues, IL 6, IL 10, cGMP, NO, H2 S, FSH, LH, and testosterone levels were measured by ELISA. Histopathological examination with H&E staining, as well as immunohistochemical staining for acrolein in bladder and caspase-3 and APAF-1 in testis were performed. Results: NaHS prevented the increased IL 6 and IL 10 values induced by CP as well as prevented the decrease in cGMP values associated with CP. There was no significant change in FSH values, but the LH value, which increased with CP, decreased with 25, 50, and 100 µmol/kg NaHS. In contrast, testosterone decreased in the CP group and increased in the treatment groups. NaHS was effective in many biochemical and histopathological parameters at 25 and 50 µmol/kg doses, and this effect decreased at 100 µmol/kg dose. Conclusion: H2 S has a protective and therapeutic effect on hemorrhagic cystitis and testicular dysfunction induced by cyclophosphamide. It can be suggested that H2 S is a promising molecule in facilitating cancer treatment.

Keywords: Cyclophosphamide, hydrogen sulfide, testis, bladder

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