Effect of ghrelin on total antioxidant capacity, lipid peroxidation, sperm parameters and fertility in mice against oxidative damage caused by cyclophosphamide

Abstract

Cyclophosphamide is a drug used for chemotherapy and as an immune-suppressive in the organ transplantation. Despite its many clinical implications in the treatment of cancers, this drug has toxic effects on the reproductive system. This study aimed to evaluate the effect of ghrelin against the damages caused by cyclophosphamide. In this experimental study, 40 male mice were randomly divided into four groups: (i) control; (ii) cyclophosphamide; (iii) cyclophosphamide + ghrelin; and (iv) ghrelin. Cyclophosphamide (100 mg/kg body weight), once a week, and ghrelin (80 μg/kg body weight), daily, were administered intraperitoneally for 5 weeks. After 5 weeks, the epididymides were removed and the lipid peroxidation, total antioxidant capacity and sperm parameters were examined. The fertility rate was evaluated by performance in vitro fertilisation. In the mice exposed to cyclophosphamide, the number of spermatozoa and viability, as well as total antioxidant capacity, decreased significantly (p < .05). The increase in the abnormal sperm and MDA levels was observed (p < .05). In addition, the fertility rate decreased in this group, while the use of ghrelin significantly improved the above disorders in the treatment group (p < .05). The findings of this study showed that ghrelin attenuates negative effects caused by cyclophosphamide in the sperm parameters and enhances the fertility.

Relationships between Ghrelin and Obestatin with MDA, Proinflammatory Cytokines, GSH/GSSG Ratio, Catalase Activity, and Semen Parameters in Infertile Patients with Leukocytospermia and Varicocele

“…In a rat model of varicocele, Asadi et al [45] demonstrated that ghrelin can decrease the oxidative stress (evaluated by means of MDA) caused by varicocele and enhance the activity of antioxidant enzymes. In addition, ghrelin attenuates the negative effects of cyclophosphamide, a chemotherapeutic and immune-suppressor drug, upon sperm parameters by reducing oxidative stress and LPO of sperm membranes and by enhancing the antioxidant activity [18]. These recent reports are extremely in accordance with our observations made in human semen.…”

“…Regarding the reproductive system, a protective activity of ghrelin was observed in different researches, performed in animal models, demonstrating that this peptide can decrease the testicular damages [17, 42–44]. Recent studies deal with the defensive role of ghrelin that can exert beneficial activity on redox imbalance for its anti-inflammatory and antioxidant properties also in the male reproductive system [18, 45–47]. In a rat model of varicocele, Asadi et al [45] demonstrated that ghrelin can decrease the oxidative stress (evaluated by means of MDA) caused by varicocele and enhance the activity of antioxidant enzymes.…”

“…On the other hand, very little is known about obestatin, which was observed for the first time in rat Leydig cells [15]. Different animal models of testicular damage have been used to demonstrate the protective effect of ghrelin towards the oxidative stress [16–18]. The results suggested that the presence of such peptide in the reproductive sphere may play a new important role.…”

Protective effect of ghrelin on testicular damages caused by chronic hypoxia in rats: A histopathological study

“…This role of ghrelin is presumably due to its antioxidative activity. In previous studies, it has been proved that the administration of ghrelin can prevent destructive effects of various factors such as chemotherapy (Salimnejad et al., ), cryptorchidism (Kheradmand et al., ) and cadmium toxicity (Kheradmand et al., ).…”

“…Previous studies on the effects of ghrelin on different tissues under hypoxic conditions have recognised that it can significantly reduce the harmful effects induced by hypoxia and protect the tissue against damages caused by oxidative stress induced by hypoxia (Aliparasti, Alipour, Almasi, & Feizi, ; Bavil et al., ; Omrani, Alipour, & Mohaddes, ). Ghrelin does this process by reducing lipid peroxidation and also increasing total antioxidant capacity (Salimnejad et al., ). In the current study, ghrelin has likely prevented the effects of hypoxia on spermatogenesis.…”