Role of melatonin in mitigating chemotherapy-induced testicular dysfunction in Wistar rats

Abstract

Testicular cancer is the most common cancer affecting men of reproductive age, and its incidence is increasing steadily. A regimen of cisplatin (P), vinblastin (V) and bleomycin (B) (PVB) is the standard chemotherapy for testicular cancer. Though PVB-based chemotherapy has been widely used against germ cell tumors, it is associated with induction of oxidative toxicity and a transient or permanent loss of fertility. However, the mechanism of action of PVB on the testis is not thoroughly elucidated. Using a rat model, we investigated the persistence of the effects of PVB on steroidogenesis, spermatogenesis and testicular oxidative status and architecture. Further, we have also studied whether administration of melatonin has any protective effect on testicular physiology in the PVB-treated rats, since melatonin exerts influence on the antioxidant defense system. The body weight of the PVB-treated rats did not show significant change as compared with the control group. Significant decrease in the weight of the testis was observed with a reduction in volume in the PVB-treated rats. Administration of PVB caused a reduction in the testicular steroidogenesis and spermatogenesis. The circulatory levels of testosterone were also significantly reduced with an elevation of FSH and LH in the PVB-treated rats. Testicular architecture was severely affected with a reduction in seminiferous tubule diameter and epithelial height. The activities of superoxide dismutase and catalase were decreased while the levels of lipid peroxidation increased significantly in the testis of the PVB-treated rats indicating depletion of antioxidant defence system and elevation of oxidative stress. Co-administration of melatonin mitigated these changes in the PVB-treated rats.

Synergistic effect of melatonin and ghrelin in preventing cisplatin‐induced ovarian damage via regulation of FOXO3a phosphorylation and binding to the p27Kip1 promoter in primordial follicles

“…In addition, Codenotti et al. showed that melatonin ameliorates chemotherapy‐induced testicular dysfunction in rats treated with cisplatin, vinblastine, and bleomycin …”

“…Our research focuses on developing adjuvants to preserve fertility in female cancer patients. Studies have shown that melatonin and ghrelin provide partial protection against cisplatin‐induced damage to the ovaries and testes . However, the administration of either drug alone does not provide adequate protection against cisplatin‐induced infertility and the effect of ghrelin on the ovaries remains uncharacterized.…”

The antiapoptotic and antioxidant effects of eugenol against cisplatin‐induced testicular damage in the experimental model

“…Testicular dysfunction or damage is among the critical side effects of chemotherapeutic drugs such as cisplatin (Madhu, Reddy, & Reddy, ). Cisplatin‐induced toxicity is consisted by increased formation of reactive oxygen species (ROS) and reduced generation or activity of antioxidant enzymes (Ekinci Akdemir et al, ).…”

Dietary Sources and Bioactivities of Melatonin

“…It was also found that melatonin-based creams could significantly lower the occurrence of acute radiation dermatitis in a double-blind randomized trial [244]. It was revealed that melatonin, as a powerful antioxidant, played a protective role at 10 mg/kg in rats to alleviate the testicular dysfunction induced by chemotherapy against testicular cancer [245], which is one of the most common cancers in men of reproductive age with a steadily increasing incidence [227]. Another in vivo study reported that melatonin (25 mg/kg) could synergize the chemotherapeutic effect of 5-fluorouracil (one of the most commonly used chemotherapeutic agents to treat colon cancer) in mice with colon cancer, by promoting the activation of the caspase/poly-ADP-ribose polymerase (PARP)-dependent apoptosis pathway, inhibiting PI3K/AKT and NF-κB/iNOS signaling pathways.…”