L-carnitine could suppress cyclophosphamide induced oocyte apoptosis in mice

Background: With the advent of early cancer diagnosis and more effective individualized cancer treatments, a growing number of young cancer patients become long-term survivors during their reproductive years. Cyclophosphamide (CP) is one of the most effective alkylating agents that used for cancer therapy which can be mostly attributed to ovarian toxicity and depletion of the oocyte. One of the options for fertility preservation in female cancer patients uses Antioxidant. Antioxidant that can prevent the loss of follicles at the time of treatment would provide significant advantages over existing fertility preservation techniques in that they would be suitable for patients of all ages and life stages. L-carnitine (LC) acts as an antioxidant that neutralizes the free radicals especially superoxide anion and protects cell against oxidative damage. L-carnitine should be viewed as a leading candidate and must be given along cyclophosphamide to block their ovarian toxicities.Objective: In our current study, we examined the antiapoptosis effect of L-carnitine on oocyte in Cyclophosphamide Treated Mice.Materials and Methods: Female NMRI mice were divided into four groups (N=10): control group was intraperitoneally injected with normal saline for 10 consecutive days; group CP was an intraperitoneal injected single dose of Cyclophosphamide (75mg/kg); LC and CP+CL groups were injected with L-carnitine (200 mg/kg, i.p.) for 10 consecutive days and the CP+CL group was received single dose of Cyclophosphamide (75 mg/kg) On the tenth day. Female NMRI mice were injected with 8 IU pregnant mare serum gonadotropin (PMSG) followed by 8 IU human chorionic gonadotropin 48 hours later and then oocytes were retrieved 14 hours later. Then the Caspase3, BAX, and Bcl-2 expression were evaluated by Real-time PCR. Moreover, intracellular ROS level was examined by DCFH-DA fluorescence intensity.Results: LC can enhance significantly (p<0.05) Bcl-2 gene expression and decrease Caspase3 and BAX genes expression in LC + CP group in comparison with the CP group. and also L-carnitine can significantly (p<0.05) decrease the mean of intracellular ROS in CP+LC group in comparison with CP group (28.77 vs. 42.58).Conclusion: The results of our study showed the effective role of L-Carnitine in the removal of ROS produced in the oocytes encountered with the cyclophosphamide chemotherapy drug, therefore, L-carnitine can be used as an option to protect the oocytes against damage Induced by cyclophosphamide.

Keywords:

L-carnitine , Cyclophosphamide , Oocyte , Apoptosis