J Gynecol Oncol.  2013 Apr;24(2):177-185. 10.3802/jgo.2013.24.2.177.

The mechanism of mesna in protection from cisplatin-induced ovarian damage in female rats

• Li X
• Yang S
• Lv X
• Sun H
• Weng J
• Liang Y
• Zhou D

• KMID: 2288550
• DOI: http://doi.org/10.3802/jgo.2013.24.2.177

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.

Keyword

Anti-Mullerian hormone; Cisplatin; Mesna; Ovarian reserve; Oxidative stress

MeSH Terms

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
Anti-Mullerian Hormone
Cisplatin
Glutathione
Malondialdehyde
Mesna
Superoxide Dismutase

Figure

• 

  Fig. 1 Representative immunofluorescence images of follicles in normal saline control (NS), mesna (M), low-dose cisplatin (CL), CL+M, high-dose cisplatin (CH), and CH+M groups, showing anti-Müllerian hormone (AMH) expression. I0, no staining; I1, weak staining; I2, moderate staining; I3, strong staining. D1, ≤50% of the structure staining; and D2, ≥50% of the structure staining. (B) Percentage of AMH-positive follicles in NS, M, CL, CL+M, CH, and CH+M groups. p<0.05 for NS vs. CH, NS vs. CL, M vs. CH, C vs. CL, CL vs. CH, and CL vs. CL+M.

• 

  Fig. 2 Effects of cisplatin or cisplatin+mesna on the viability of HepG2 cells at different dose and treatment time [24 hr (A), 48 hr (B), 72 hr (C)] by methyl thiazolyl tetrazolium assay. *Compared to corresponding control, p<0.05.There is no significant difference in the viability of HepG2 cells between cisplatin group and cisplatin+mesna group.

• 

  Fig. 3 (A) Malondialdehyde (MDA) level in normal saline control (NS), mesna (M), low-dose cisplatin (CL), CL+M, high-dose cisplatin (CH), and CH+M groups. p<0.05 for NS vs. CH, NS vs. CL, M vs. CH, M vs. CL, CL vs. CH, and CH vs. CH+M. (B) Superoxide dismutase (SOD) activity in NS, M, CL, CL+M, CH and CH+M groups. p<0.05 for NS vs. CH, NS vs. CL, M vs. CH, M vs. CL, CL vs. CH, CL vs. CL+M, and CH vs. CH+M. (C) Glutathione (GSH) level in NS, M, CL, CL+M, CH and CH+M groups. p<0.05 for NS vs. CH, NS vs. CL, M vs. CH, M vs. CL, CL vs. CL+M, and CH vs. CH+M.

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