Backround and 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, anti-inflammatory 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. Material and methods Rats were divided into 5 groups (n = 8): control, CP, NaHS25 μmol / kg, NaHS50 μmol / kg, 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. 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 2 / 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 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.

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Our findings indicate that therapy of multiple sclerosis with glatiramer acetate presumably involves the compensation of altered apoptosis in T-helper lymphocytes.

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Aim To investigate whether recombinant klotho given concomitantly with cisplatin is effective in preventing cisplatin‐induced ovarian damage. Methods Thirty‐two adult female mice were divided into four groups. Saline was given to the first group, cisplatin to the second group, recombinant mouse klotho to the third group, and recombinant mouse klotho + cisplatin to the fourth group. The removed ovarian tissues were examined and groups were compared histologically and immunohistochemical examination for antimullerian hormone (AMH), superoxide dismutase (SOD) and catalase expression were done. Glutathione peroxidase (GPx) and glutathione reductase (GR) activities were measured by ELISA. Results Ovarian tissue weight, primary and secondary follicle counts were higher in cisplatin + recombinant klotho group compared to cisplatin group in our study (respectively p < 0.0001, p < 0.0001, and p = 0.010). Injury scores (stromal congestion, edema and infiltration, follicular degeneration scores and edema in corpus luteum scores) were similar between cisplatin and cisplatin + recombinant klotho groups (all p > 0.05). AMH staining intensities were similar between cisplatin and cisplatin + recombinant klotho groups (p = 0.925). There was no difference between the groups in terms of SOD, GPx, and GR (p > 0.05). Conclusions The recombinant klotho administered before cisplatin could partially protect the ovarian tissue from cisplatin‐induced ovarian damage considering that there was no difference in histologic injury score parameters, AMH staining intensity and oxidative stress markers between cisplatin and cisplatin plus klotho groups except that klotho preserved follicules to some extent. The antioxidant mechanism of action of klotho may not be the primary protection mechanism in cisplatin induced ovarian injury.

Background: Cyclophosphamide is a commonly used anticancer and immunosuppressive agent; however, hepatotoxicity is one of its severe toxicities. Hydrogen sulfide is a gaseous signaling molecule that plays crucial regulatory roles in various physiological functions. This study aimed to evaluate the hepatoprotective effect of hydrogen sulfide against cyclophosphamide-induced hepatic damage in rats. Methods: Hepatotoxicity was induced by the single intraperitoneal administration of cyclophosphamide (200 mg/kg). Sprague–Dawley rats were treated by hydrogen sulfide donor, sodium hydrosulfide (25, 50, and 100 µmol/kg, intraperitoneal) 7 days before and 7 days after the administration of a single intraperitoneal injection of cyclophosphamide (200 mg/kg). Cyclophosphamide-induced hepatotoxicity was evaluated by serum and tissue biochemical and histopathological assessments. The levels of hydrogen sulfide, nitric oxide, cyclic guanosine monophosphate, interleukin 6, and interleukin 10 in liver homogenates were also determined by ELISA. One-way analysis of variance and Kruskal–Wallis tests were used as statistical analyses. Results: Cyclophosphamide increased liver function enzymes (alanine aminotransferase and aspartate aminotransferase), immunoreactivity to caspase-3 and Apaf-1, and proinflammatory cytokines. Cyclophosphamide also induced histopathological alterations including pycnotic nucleus with eosinophilic cytoplasm, increased sinusoidal dilatation, congestion, and edema. Hydrogen sulfide co-treatment significantly reduced cyclophosphamide-induced inflammation, histological alterations, and apoptosis in the liver. 50 mg/kg sodium hydrosulfide was more effective against cyclophosphamide-induced hepatotoxicity. Conclusion: In conclusion, hydrogen sulfide with its anti-inflammatory and anti-apoptotic effects seems to be beneficial as an adjunct to cyclophosphamide treatment to reduce cyclophosphamide-induced hepatotoxicity and thereby can be suggested as a promising agent to increase the therapeutic efficacy of cyclophosphamide.