期刊
JOURNAL OF GYNECOLOGIC ONCOLOGY
卷 24, 期 2, 页码 177-185出版社
KOREAN SOC GYNECOLOGY ONCOLOGY & COLPOSCOPY
DOI: 10.3802/jgo.2013.24.2.177
关键词
Anti-Mullerian hormone; Cisplatin; Mesna; Ovarian reserve; Oxidative stress
资金
- National Science Foundation of China (NSFC) [30971349, 81101769, 81001044]
- Funding Project for Academic Human Resources Development in Institutions of Higher Learning under the Jurisdiction of Beijing Municipality (IHLB) [PHR201007113]
- Science Foundation of Capital Medical University [2012ZR07]
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 (C-L), high-dose cisplatin (C-H), C-L plus mesna (C-L+M), and C-H plus mesna (C-H+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.
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