Department of Pharmacology, Faculty of Medicine, Kütahya Health Sciences University, Kütahya, Turkey
Department of Histology and Embriology, Faculty of Medicine, Kütahya Health Sciences University, Kütahya, Turkey
Turk J Med Sci. 2021 Jun 28;51(3):1531-1543. doi: 10.3906/sag-2003-10.
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 (H2S) is a gaseous mediator and is suggested to have antioxidant, antiinflammatory, and antiapoptotic effects. In this study, dose-dependent effects of H2S donor sodium hydrosulfide (NaHS) on cyclophosphamide-induced hemorrhagic cystitis and testicular dysfunction were investigated in rats.
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, H2S, 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.
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.
H2S has a protective and therapeutic effect on hemorrhagic cystitis and testicular dysfunction induced by cyclophosphamide. It can be suggested that H2S is a promising molecule in facilitating cancer treatment.
背景/目的：环磷酰胺（CP）是一种用于治疗多种恶性疾病的药物。然而，它会引起严重的副作用，如出血性膀胱炎和男性不育。硫化氢（H2S）是一种气态介质，具有抗氧化、抗炎和抗凋亡作用。在这项研究中，研究了 H2S 供体硫氢化钠（NaHS）对大鼠环磷酰胺诱导的出血性膀胱炎和睾丸功能障碍的剂量依赖性影响。
大鼠分为 5 组（n = 8）：对照组、CP 组、NaHS25 μmol/kg 组、NaHS50 μmol/kg 组和 NaHS100 μmol/kg 组。腹腔内（ip）治疗 7 天后，第 8 天给予 CP 200 mg/kg 单次 ip 剂量。然后继续治疗 7 天。通过 ELISA 测量膀胱和睾丸组织中的 IL6、IL10、cGMP、NO、H2S、FSH、LH 和睾酮水平。进行 H&E 染色的组织病理学检查以及膀胱中的丙烯醛和睾丸中的 caspase-3 和 APAF-1 的免疫组织化学染色。
NaHS 可预防 CP 诱导的 IL6 和 IL10 值升高，并预防与 CP 相关的 cGMP 值降低。FSH 值没有显著变化，但 CP 增加的 LH 值随 25、50 和 100 μmol/kg NaHS 降低。相比之下，CP 组的睾酮降低，治疗组的睾酮升高。NaHS 在 25 和 50 μmol/kg 剂量下对许多生化和组织病理学参数有效，而在 100 μmol/kg 剂量下效果降低。
H2S 对环磷酰胺诱导的出血性膀胱炎和睾丸功能障碍具有保护和治疗作用。可以认为 H2S 是促进癌症治疗的有前途的分子。
