Melatonin Protects Against Epirubicin-Induced Ovarian Damage

Abstract

One major side effect of chemotherapy young cancer women suffer is ovarian damage. Therefore, it is necessary to study the pathogenesis of chemotherapeutic drugs for developing pharmaceutical agents to preserve fertility. Epirubicin is one of the commonly used chemotherapy drugs for breast cancer patients. This research explored the side effects of epirubicin in mice. We found that epirubicin significantly reduced the body weight, the weight of the ovaries and uteri, and the pups' number, while melatonin is extremely resistant to oxidation, significantly reduced these damages. Moreover, treatment together with melatonin prevented epirubicin caused decrease of E2 and progesterone and the loss of follicles. Mechanism study discovered that melatonin significantly reduced the levels of proapoptotic genes p53, Caspase3, and Caspase9 while upregulated antiapoptotic factors Bcl-2, Bcl2l1, and antioxidant genes superoxide dismutase 1 and catalase compared with epirubicin group. In addition, melatonin markedly reduced reactive oxygen species (ROS) and the transcription of Caspase12 and Chop, which is vital in endoplasmic reticulum stress (ERS) mediated apoptosis. These results indicate melatonin protects against epirubicin caused ovarian damage through reducing ROS caused ERS. Therefore, melatonin has therapeutic potential for the protection of ovarian function and preservation of fertility during chemotherapy. Funding Statement: This study was supported by grants from National Key R&D Program of China (2017YFC1001403), and NSFC (31871512 and 31671199) to C. Z. Support was also obtained by grant from the Major Program of the National Natural Science Foundation of China (NSFC) (81490743) to Z.-J.C., and by the Shanghai Commission of Science and Technology (17DZ2271100). Declaration of Interests: The authors declare that there are no conflicts of interest. Ethics Approval Statement: Mice were treated according to the Guidelines of Shandong Normal University for the Care and Use of Laboratory Animals.