The mechanism of mesna in protection from cisplatin-induced ovarian damage in female rats.
10.3802/jgo.2013.24.2.177
- Author:
Xiaohuan LI
1
;
Shu YANG
;
Xiangyang LV
;
Haimei SUN
;
Jing WENG
;
Yuanjing LIANG
;
Deshan ZHOU
Author Information
1. Department of Histology and Embryology, School of Basic Medical Sciences, Capital Medical University, Beijing, China. zhoudeshan2008@163.com
- Publication Type:Original Article
- Keywords:
Anti-Mullerian hormone;
Cisplatin;
Mesna;
Ovarian reserve;
Oxidative stress
- MeSH:
Adult;
Animals;
Anti-Mullerian Hormone;
Cisplatin;
Female;
Fertility;
Glutathione;
Granulosa Cells;
Hep G2 Cells;
Humans;
Lipid Peroxidation;
Malondialdehyde;
Menopause, Premature;
Mesna;
Ovary;
Oxidative Stress;
Rats;
Rats, Sprague-Dawley;
Superoxide Dismutase
- From:Journal of Gynecologic Oncology
2013;24(2):177-185
- CountryRepublic of Korea
- Language:English
-
Abstract:
OBJECTIVE: Cisplatin is a widely used chemotherapeutic agent in the treatment of cancers in clinic; but it often induces adverse effects on ovarian functions such as reduced fertility and premature menopause. Mesna could attenuate the cisplatin-induced ovarian damages; however, the underlying mechanism is still unknown. This study aimed to figure out the underlying mechanism of the protection of mesna for ovaries against cisplatin therapy in cancers. METHODS: We performed female adult Sprague-Dawley rats into normal saline control (NS), low-dose cisplatin (CL), high-dose cisplatin (CH), CL plus mesna (CL+M), and CH plus mesna (CH+M) groups and detected anti-Mullerian hormone (AMH)-positive follicle, oxidative stress status and anti-oxidative capability in ovaries. RESULTS: AMH-positive follicles were significantly decreased after cisplatin administration, which was significantly reversed when mesna was co-administered with cisplatin. The end product of lipid peroxidation, malondialdehyde (MDA), was significantly increased, but the anti-oxidative enzymatic activity of superoxide dismutase (SOD) and glutathione (GSH) were significantly decreased in cisplatin groups when compared with NS group. In contrast, after co-administration of cisplatin with mesna, MDA was significantly decreased whereas the activity of SOD and the concentration of GSH were increased. Moreover, mesna did not decrease the anti-tumor property of cisplatin in HePG2 cell lines. CONCLUSION: Cisplatin damages the granulosa cells by oxidative stress to deplete the ovarian reserve and mesna could protect ovarian reserve through anti-oxidation. These results might highlight the mechanism of the protection of mesna for ovarian reserve and open an avenue for the application of mesna as a protective additive in cisplatin chemotherapy in clinical practise.
