title: The mechanism of mesna in protection from cisplatin-induced ovarian damage in female rats.
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-Müllerian 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.
  
  
  CONCLUSIONS
  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.
authors: Department of Histology and Embryology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
authors: Xiaohuan
authors: X
authors: Li
authors: Shu
authors: S
authors: Yang
authors: Xiangyang
authors: X
authors: Lv
authors: Haimei
authors: H
authors: Sun
authors: Jing
authors: J
authors: Weng
authors: Yuanjing
authors: Y
authors: Liang
authors: Deshan
authors: D
authors: Zhou
keywords: Anti-Müllerian hormone; Cisplatin; Mesna; Ovarian reserve; Oxidative stress
references: Anticancer Agents Med Chem. 2007 Jan;7(1):3-18
references: 17266502
references: Eur J Obstet Gynecol Reprod Biol. 2007 Feb;130(2):148-55
references: 16979280
references: Fertil Steril. 2010 Jun;94(1):156-66
references: 19342041
references: Fertil Steril. 2009 Aug;92(2):417-27
references: 18774559
references: Am J Obstet Gynecol. 2008 Apr;198(4):463.e1-6; discussion 463.e6-7
references: 18395042
references: J Clin Endocrinol Metab. 2005 Oct;90(10):5536-43
references: 16030171
references: Eur J Cancer. 2004 Nov;40(16):2445-51
references: 15519518
references: Hum Reprod Update. 2005 Jan-Feb;11(1):69-89
references: 15569700
references: Semin Oncol. 1998 Oct;25(5):584-99
references: 9783598
references: Exp Toxicol Pathol. 2009 May;61(3):223-42
references: 18986801
references: J Surg Res. 2004 Sep;121(1):84-91
references: 15313380
references: Med Oncol. 2004;21(1):9-20
references: 15034209
references: Mol Cell Endocrinol. 2000 Nov 27;169(1-2):123-31
references: 11155944
references: Reproduction. 2006 Jan;131(1):1-9
references: 16388003
references: Support Care Cancer. 1998 Mar;6(2):144-54
references: 9540174
references: Acta Anaesthesiol Scand. 2000 Jul;44(6):770
references: 10903025
references: Biol Reprod. 1995 Aug;53(2):295-301
references: 7492681
references: J Pharmacol Exp Ther. 2003 Jun;305(3):1183-90
references: 12649298
references: Eur J Cancer. 1998 Sep;34(10):1522-34
references: 9893623
references: Biochem Biophys Res Commun. 2006 Sep 22;348(2):337-44
references: 16875679
references: Endocr Rev. 1993 Apr;14(2):152-64
references: 8325249
references: Clin Endocrinol (Oxf). 1997 Feb;46(2):217-9
references: 9135705
references: Toxicology. 2004 Feb 15;195(2-3):221-30
references: 14751677
references: Life Sci. 2004 Sep 24;75(19):2329-40
references: 15350830
references: Biomed Pharmacother. 2009 Feb;63(2):79-85
references: 18819770
references: Fertil Steril. 2008 Aug;90(2):395-400
references: 17919608
references: Aust N Z J Obstet Gynaecol. 2004 Feb;44(1):6-9
references: 15089860
references: J Natl Cancer Inst Monogr. 2005;(34):18-21
references: 15784815
references: Anticancer Res. 2001 Mar-Apr;21(2A):1225-9
references: 11396168
references: Pharmacol Res. 2001 Feb;43(2):145-50
references: 11243715
references: J Appl Toxicol. 2013 Feb;33(2):125-33
references: 22147442
references: Mol Cell Endocrinol. 2003 Dec 15;211(1-2):85-90
references: 14656480
references: J Natl Cancer Inst. 2006 Jul 5;98(13):890-6
references: 16818852
references: Eur J Cancer. 1997 Aug;33(9):1393-9
references: 9337680
references: Cancer Res. 1993 May 1;53(9):2133-9
references: 8481916
references: Mol Cell Endocrinol. 2005 Apr 29;234(1-2):81-6
references: 15836956
references: Med Pediatr Oncol. 1989;17(5):409-13
references: 2507885
references: Hear Res. 2007 Apr;226(1-2):157-67
references: 17113254