The effect of glutathione on sperm dna fragmentation in rat models of bleomycin etoposide cis-platin treatment

Testicular cancer is one of the most common malignant tumors in young men of reproductive age (20-40 years). The combination of cis-platin-based chemotherapeutic agents and specific Bleomycin, Etoposide and cis-platin (BEP) used in its treatment increases survival and causes damage to healthy tissues. One of the important tissues in which it is damaged is testicular tissue and sperm cells. In this study, we investigated the protective effect of glutathione (GSH) application on sperm DNA integrity and testicular histomorphology damage caused by BEP treatment in rats. Twenty two-week-old male rats of reproductive age (n=24) were randomly divided into 3 groups as control, BEP and BEP+GSH, 8 rats in each group. The BEP group was administered intraperitoneally for 9 weeks, 3 cycles of 21 days each, according to the BEP doses determined in the preliminary study (0.083; 0.83; 0.17 mg/kg). Glutathione 200 mg/kg was administered to the BEP+GSH group on the 1st and 4th days of the week for 9 weeks, together with the chemotherapeutic treatment applied to the BEP group. In the control group, 0.9% NaCl was given intraperitoneally on the days when the other groups were treated with drugs. When the weight gains of the groups were compared, the weight gain of the BEP+GSH group was not significant compared to the weight gain of the BEP group (p=0.921). The increase in the control group was higher than the BEP group and BEP+GSH group (p˂0.027, p˂0.012). Similarly, left testis weights (p˂0.017; p˂0.003), left epididymis weights (p˂0.029; p˂0.037), right epididymis weights (p˂0.002; p˂0.004), testicular weight indices (p˂0) of the control group ,0017; p˂0.001) were higher than BEP group and BEP+GSH group. Morphological anomaly rate and sperm DNA fragmentation were found to be considerably lower in the BEP+GSH group and the control group compared to the BEP group (p˂0.001; p˂0.001). Serum testosterone level and sperm count of BEP+GSH group and control group were higher than BEP group. It was observed that seminiferous tubule epithelial thicknesses and Johnsen scores in testicles were thicker in the control group and BEP+GSH group compared to the BEP group (p<0.000). In conclusion, GSH treatment improved sperm count, sperm morphology, and testicular morphology in BEP-treated rats, and decreased sperm DNA fragmentation, thus potentially improving male infertility caused by chemotherapeutics.