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Dergiler / Journal of Experimental and Clinical Medicine / 2026 / Volume: 38 Issue: 2

Evaluation of protective effects of mirtazapine and mesna on cisplatin-induced ovarian damage in rats

Ali Doğukan Anğın(Health Sciences University Kartal Training and Research Hospital, Obstetrics and Gynecology Clinic, Istanbul, Turkey.)0000-0003-1954-8546
Muhammet Ali Oruç(Department of Family Medicine, Faculty of Medicine, Ahi Evran University, Kırsehir, Turkey;)0000-0002-4320-8579
Önder Sakin(Health Sciences University Kartal Dr.Lutfi Kirdar Training and Research Hospital, Obstetrics and Gynecology Clinic, Istanbul, Turkey)0000-0001-6036-9975
Emine Eda Akalın(Health Sciences University Kartal Training and Research Hospital, Obstetrics and Gynecology Clinic, Istanbul, Turkey.)0000-0002-3593-5063
Muzaffer Çıkman(Health Sciences University Kartal Dr.Lutfi Kirdar Training and Research Hospital, Obstetrics and Gynecology Clinic, Istanbul, Turkey)0000-0003-2485-568X
Kayhan Başak(Health Sciences University Kartal Dr.Lutfi Kirdar Training and Research Hospital, Pathology Clinic, Istanbul, Turkey;)0000-0003-1960-8924
Yasemin Alan(Department of Obstetrics and Gynecology, İzmir Metropolitan Municipality Eşrefpaşa Hospital, İzmir, Turkey;)0000-0003-2680-814X
Asuman Orçun(Health Sciences University Kartal Dr.Lutfi Kirdar Training and Research Hospital, Biochemistry Clinic, Istanbul, Turkey;)0000-0002-5155-3591
Murat Alan(Department of Obstetrics and Gynecology, Universty of Health Sciences Tepecik Education and Research Hospital, İzmir, Turkey.)
Sayfa
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Yayın Tarihi
2021-04-03
DOI
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⚡ TL;DR(1 Cümlede Hızlı Çıkarım)

Conclusion: It was concluded that mesna and mirtazapine were not effective in preventing ovarian damage due to cisplatin.

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Amaç & Hipotez:Evaluation of protective effects of mirtazapine and mesna on cisplatin-induced ovarian damage in rats Objective: To evaluate whether mirtazapine and mesna have protective effects on cisplatin-induced ovarian injury.
📊
Temel Bulgular & Veri:Methods: A total of 32 female Wistar Albino rats were divided into 4 groups (8 rats per group) and included in the study.
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Sonuç & Katkı:Conclusion: It was concluded that mesna and mirtazapine were not effective in preventing ovarian damage due to cisplatin.
🔬Tür:Research Article
📍Kapsam:Genişletilmiş Akademik Örneklem
⚙️Değişkenler:Cisplatin · mirtazapine · mesna

Abstract

Evaluation of protective effects of mirtazapine and mesna on cisplatin-induced ovarian damage in rats Objective: To evaluate whether mirtazapine and mesna have protective effects on cisplatin-induced ovarian injury. Methods: A total of 32 female Wistar Albino rats were divided into 4 groups (8 rats per group) and included in the study. No medication was administered to the first group; only intervention was that their ovaries were removed and anti-mullerian hormone (AMH) values were measured. The second group received intramuscular cisplatin at a single dose of 7.5 mg/kg. The third group received a single dose of 200 mg/kg mesna intraperitoneally, and 30 minutes later, a single dose of 7.5 mg/kg intramuscular cisplatin was administered. The fourth group received oral 30 mg/kg mirtazapine, and 60 minutes later, a single dose of 7.5 mg/kg intramuscular cisplatin was administered. Oral 30 mg/kg mirtazapine was continued for ten days. Ovaries and AMH values of all groups were evaluated at the end of tenth day. Results: In the cisplatin group when compared to normal ovarian tissue total histopathological damage score increased (p=0.037), preantral follicle count decreased (p=0.003) and AMH levels decreased (p<0.001). In the cisplatin+mesna group total ovarian damage score was also increased (p=0.005), preantral and antral follicles decreased (p<0.001 and p=0.001, respectively), and AMH levels decreased (p<0.001). In the cisplatin+mirtazapine group, total ovarian damage score (p <0.001), preantral follicle count (p = 0.002) and AMH values were decreased (p <0.001). Conclusion: It was concluded that mesna and mirtazapine were not effective in preventing ovarian damage due to cisplatin.

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Bu Makaleye Atıf Yap

Anğın, A. D., Oruç, M. A., Sakin, Ö., Akalın, E. E., Çıkman, M., Başak, K., Alan, Y., Orçun, A., Alan, M. (2021). Evaluation of protective effects of mirtazapine and mesna on cisplatin-induced ovarian damage in rats. Journal of Experimental and Clinical Medicine, Volume: 38 Issue: 2. https://ajindex.com/articles/1423278

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Kaynakça (64)

  1. Altuner, D., Gulaboglu, M., Yapca, O.E., Cetin, N.,2013. The effect of mirtazapine on cisplatin-induced oxidative damage and infertility in rat ovaries. The Scientific World Journal. 2013:327240. Berger, M.M., Shenkin, A., Revelly, J.P., Roberts, E., Cayeux, M.C., Baines, M., et al.,2004. Copper, selenium, zinc, and thiamine balances during continuous venovenous hemodiafiltration in critically ill patients. The American Journal of Clinical Nutrition. 80(2):410-6.
  2. Bilici, M., Ozturk, C., Dursun, H., Albayrak, F., Saglam, M.B., Uyanik, A., et al.,2009. Protective effect of mirtazapine on indomethacin-induced ulcer in rats and its relationship with oxidant and antioxidant parameters. Digestive Diseases and Sciences. 54(9):1868-75.
  3. Celik, O., Turkoz, Y., Hascalik, S., Hascalik, M., Cigremis, Y., Mizrak, B., et al.,2004. The protective effect of caffeic acid phenethyl ester on ischemia-reperfusion injury in rat ovary. European Journal of Obstetrics, Gynecology, and Reproductive Biology. 117(2):183-8.
  4. Cheki, M., Ghasemi, M.S., Rezaei, R. A., Erfani, M. N.,2019. Metformin attenuates cisplatin-induced genotoxicity and apoptosis in rat bone marrow cells. Drug and Chemical Toxicology. 2019:1-8.
  5. Domitrovic, R., Potocnjak, I., Crncevic-Orlic, Z., Skoda, M.,2014. Nephroprotective activities of rosmarinic acid against cisplatin-induced kidney injury in mice. Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association. 66:321-8.
  6. Gulec, M., Oral, E., Dursun, O.B., Yucel, A., Hacimuftuoglu, A., Akcay, F., et al.,2013. Mirtazapine protects against cisplatin-induced oxidative stress and DNA damage in the rat brain. Psychiatry and Clinical Neurosciences. 67(1):50-8.
  7. Gulec, M., Selvi, Y., Boysan, M., Aydin, A., Besiroglu, L., Agargun, M.Y.,2011. Ongoing or re-emerging subjective insomnia symptoms after full/partial remission or recovery of major depressive disorder mainly with the selective serotonin reuptake inhibitors and risk of relapse or recurrence: a 52-week follow-up study. Journal of Affective Disorders. 134(1-3):257-65.
  8. Jordan, P., Carmo-Fonseca, M.,2000. Molecular mechanisms involved in cisplatin cytotoxicity. Cellular and molecular life sciences: CMLS.57(8-9):1229-35.
  9. Jost, P., Fikrova, P., Svobodova, H., Pejchal, J., Stetina, R.,2017. Protective potential of different compounds and their combinations with MESNA against sulfur mustard-induced cytotoxicity and genotoxicity. Toxicology Letters.275:92-100.
  10. Kabasakal, L., Sehirli, A.O., Cetinel, S., Cikler, E., Gedik, N., Sener, G.,2004. Mesna (2-mercaptoethane sulfonate) prevents ischemia/reperfusion induced renal oxidative damage in rats. Life Sciences. 75(19):2329-40.
  11. Kaygusuzoglu, E., Caglayan, C., Kandemir, F.M., Yildirim, S., Kucukler, S., Kilinc, M.A., et al.,2018. Zingerone ameliorates cisplatin-induced ovarian and uterine toxicity via suppression of sex hormone imbalances, oxidative stress, inflammation and apoptosis in female wistar rats. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie.102:517-30. Khalaf,A.A., Hussein, S., Tohamy, A.F., Marouf, S., Yassa, H.D., Zaki, A.R., et al., 2019. Protective effect of Echinacea purpurea (Immulant) against cisplatin-induced immunotoxicity in rats. 2019;27(1):233-41.
  12. Kopelman, M.D., Thomson, A.D., Guerrini, I., Marshall, E.J.,2009.The Korsakoff syndrome: clinical aspects, psychology and treatment. Alcohol and Alcoholism (Oxford, Oxfordshire). 44(2):148-54.
  13. Li, X., Yang, S., Lv, X., Sun, H., Weng, J., Liang, Y., et al.,2013. The mechanism of mesna in protection from cisplatin-induced ovarian damage in female rats. Journal of Gynecologic Oncology.24(2):177-85.
  14. Morgan, S., Anderson, R.A., Gourley,C., Wallace, W.H., Spears, N.,2012. How do chemotherapeutic agents damage the ovary? Human Reproduction update.18(5):525-35.
  15. Oktay, K., Schenken, R.S., Nelson, J.F., 1995.Proliferating cell nuclear antigen marks the initiation of follicular growth in the rat. Biology of Reproduction. 53(2):295-301.
  16. Omar, H.A., Mohamed, W.R., Arafa el, S.A., Shehata, B.A., El Sherbiny, G.A., Arab, H.H., et al.,2016. Hesperidin alleviates cisplatin-induced hepatotoxicity in rats without inhibiting its antitumor activity. Pharmacological Reports: PR. 68(2):349-56.
  17. Pandir, D., Kara, O., Kara, M.,2014. Protective effect of bilberry (Vaccinium myrtillus L.) on cisplatin induced ovarian damage in rat. Cytotechnology. 66(4):677-85.
  18. Parlakgumus, H.A., Aka, B. F., Bulgan, K. E., Simsek, E., Parlakgumus, A.,2014. Atorvastatin for ovarian torsion: effects on follicle counts, AMH, and VEGF expression. European journal of Obstetrics, Gynecology, and Reproductive Biology.175:186-90.
  19. Qian, G., Dai, L., Yu, T.,2019. Thioridazine Sensitizes Cisplatin Against Chemoresistant Human Lung and Ovary Cancer Cells. DNA and Cell Biology.38(7):718-24.
  20. Roness, H., Kalich-Philosoph, L., Meirow, D., 2014.Prevention of chemotherapy-induced ovarian damage: possible roles for hormonal and non-hormonal attenuating agents. Human Reproduction Update. 20(5):759-74.
  21. Rybak, L.P., Whitworth, C.A., Mukherjea, D., Ramkumar, V.,2007. Mechanisms of cisplatin-induced ototoxicity and prevention. Hearing research.226(1-2):157-67.
  22. Saribas, G.S., Erdogan, D., Goktas, G., Akyol, S.N., Hirfanoglu, I.M., Gurgen, S.G., et al,2016. Examining the protective effects of acetyl l-carnitine on cisplatin-induced uterine tube toxicity. Journal of obstetrics and gynaecology: the journal of the Institute of Obstetrics and Gynaecology.;36(8):1086-92.
  23. Sener, M.T., Sener, E., Tok, A., Polat, B., Cinar, I., Polat, H., et al.,2012. Biochemical and histologic study of lethal cisplatin nephrotoxicity prevention by mirtazapine. Pharmacological reports: PR.64(3):594-602.
  24. Siu, L.L., Moore, M.J.,1998. Use of mesna to prevent ifosfamide-induced urotoxicity. Supportive care in cancer: official journal of the Multinational Association of Supportive Care in Cancer. 6(2):144-54.
  25. Srivastava, A.N., Gupta, A., Srivastava, S., Natu, S.M., Mittal, B., Negi, M.P., et al.,2010. Cisplatin combination chemotherapy induces oxidative stress in advance non small cell lung cancer patients. Asian Pacific journal of Cancer Prevention: APJCP.11(2):465-71.
  26. Streuli, I., Fraisse, T., Pillet, C., Ibecheole, V., Bischof, P., de Ziegler, D.,2008. Serum antimullerian hormone levels remain stable throughout the menstrual cycle and after oral or vaginal administration of synthetic sex steroids. Fertility and Sterility.90(2):395-400.
  27. Stroud, J.S., Mutch, D., Rader, J., Powell, M., Thaker, P.H., Grigsby, P.W.,2009. Effects of cancer treatment on ovarian function. Fertility and Sterility. 92(2):417-27.
  28. Visser, J.A., de Jong, F.H., Laven, J.S., Themmen, A.P.,2006. Anti-Mullerian hormone: a new marker for ovarian function. Reproduction (Cambridge, England).131(1):1-9
  29. Weijl, N.I., Hopman, G.D., Wipkink-Bakker, A., Lentjes, E.G., Berger, H.M., Cleton, F.J., et al.,1998. Cisplatin combination chemotherapy induces a fall in plasma antioxidants of cancer patients. Annals of oncology: official journal of the European Society for Medical Oncology. 1998;9(12):1331-7.
  30. Wu, Y., Ma, C., Zhao, H., Zhou, Y., Chen, Z.2018. Alleviation of endoplasmic reticulum stress protects against cisplatin-induced ovarian damage.16(1):85. Xiao, S., Zhang, J., Liu,M., Iwahata, H., Rogers, H.B., Woodruff, T.K.,2017. Doxorubicin Has Dose-Dependent Toxicity on Mouse Ovarian Follicle Development, Hormone Secretion, and Oocyte Maturation. Toxicological Sciences: an Official Journal of the Society of Toxicology. 157(2):320-9.
  31. Yeh, J., Kim, B., Liang, Y.J., Peresie, J.,2006. Mullerian inhibiting substance as a novel biomarker of cisplatin-induced ovarian damage. Biochemical and Biophysical Research Communications. 348(2):337-44.
  32. Yeh, J., Kim, B.S., Peresie, J., 2008. Protection against cisplatin-induced ovarian damage by the antioxidant sodium 2-mercaptoethanesulfonate (mesna) in female rats. American Journal of Obstetrics and Gynecology. 198(4):463.e1-6; discussion.e6-7. Yeh, J., Kim, B.S., Peresie, J.,2008. Protection against cisplatin-induced ovarian damage by the antioxidant sodium 2-mercaptoethanesulfonate (mesna) in female rats. American journal of obstetrics and gynecology.198(4):463 e1-6; discussion e6-7. Ypsilantis, P., Tentes, I., Assimakopoulos, S.F., Kortsaris, A., Scopa, C.D., Simopoulos, C.,2004. Mesna ameliorates intestinal mucosa damage after ifosfamide administration in the rabbit at a dose-related manner. The Journal of surgical research. 121(1):84-91.
  33. Altuner, D., Gulaboglu, M., Yapca, O.E., Cetin, N.,2013. The effect of mirtazapine on cisplatin-induced oxidative damage and infertility in rat ovaries. The Scientific World Journal. 2013:327240. Berger, M.M., Shenkin, A., Revelly, J.P., Roberts, E., Cayeux, M.C., Baines, M., et al.,2004. Copper, selenium, zinc, and thiamine balances during continuous venovenous hemodiafiltration in critically ill patients. The American Journal of Clinical Nutrition. 80(2):410-6.
  34. Bilici, M., Ozturk, C., Dursun, H., Albayrak, F., Saglam, M.B., Uyanik, A., et al.,2009. Protective effect of mirtazapine on indomethacin-induced ulcer in rats and its relationship with oxidant and antioxidant parameters. Digestive Diseases and Sciences. 54(9):1868-75.
  35. Celik, O., Turkoz, Y., Hascalik, S., Hascalik, M., Cigremis, Y., Mizrak, B., et al.,2004. The protective effect of caffeic acid phenethyl ester on ischemia-reperfusion injury in rat ovary. European Journal of Obstetrics, Gynecology, and Reproductive Biology. 117(2):183-8.
  36. Cheki, M., Ghasemi, M.S., Rezaei, R. A., Erfani, M. N.,2019. Metformin attenuates cisplatin-induced genotoxicity and apoptosis in rat bone marrow cells. Drug and Chemical Toxicology. 2019:1-8.
  37. Domitrovic, R., Potocnjak, I., Crncevic-Orlic, Z., Skoda, M.,2014. Nephroprotective activities of rosmarinic acid against cisplatin-induced kidney injury in mice. Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association. 66:321-8.
  38. Gulec, M., Oral, E., Dursun, O.B., Yucel, A., Hacimuftuoglu, A., Akcay, F., et al.,2013. Mirtazapine protects against cisplatin-induced oxidative stress and DNA damage in the rat brain. Psychiatry and Clinical Neurosciences. 67(1):50-8.
  39. Gulec, M., Selvi, Y., Boysan, M., Aydin, A., Besiroglu, L., Agargun, M.Y.,2011. Ongoing or re-emerging subjective insomnia symptoms after full/partial remission or recovery of major depressive disorder mainly with the selective serotonin reuptake inhibitors and risk of relapse or recurrence: a 52-week follow-up study. Journal of Affective Disorders. 134(1-3):257-65.
  40. Jordan, P., Carmo-Fonseca, M.,2000. Molecular mechanisms involved in cisplatin cytotoxicity. Cellular and molecular life sciences: CMLS.57(8-9):1229-35.
  41. Jost, P., Fikrova, P., Svobodova, H., Pejchal, J., Stetina, R.,2017. Protective potential of different compounds and their combinations with MESNA against sulfur mustard-induced cytotoxicity and genotoxicity. Toxicology Letters.275:92-100.
  42. Kabasakal, L., Sehirli, A.O., Cetinel, S., Cikler, E., Gedik, N., Sener, G.,2004. Mesna (2-mercaptoethane sulfonate) prevents ischemia/reperfusion induced renal oxidative damage in rats. Life Sciences. 75(19):2329-40.
  43. Kaygusuzoglu, E., Caglayan, C., Kandemir, F.M., Yildirim, S., Kucukler, S., Kilinc, M.A., et al.,2018. Zingerone ameliorates cisplatin-induced ovarian and uterine toxicity via suppression of sex hormone imbalances, oxidative stress, inflammation and apoptosis in female wistar rats. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie.102:517-30. Khalaf,A.A., Hussein, S., Tohamy, A.F., Marouf, S., Yassa, H.D., Zaki, A.R., et al., 2019. Protective effect of Echinacea purpurea (Immulant) against cisplatin-induced immunotoxicity in rats. 2019;27(1):233-41.
  44. Kopelman, M.D., Thomson, A.D., Guerrini, I., Marshall, E.J.,2009.The Korsakoff syndrome: clinical aspects, psychology and treatment. Alcohol and Alcoholism (Oxford, Oxfordshire). 44(2):148-54.
  45. Li, X., Yang, S., Lv, X., Sun, H., Weng, J., Liang, Y., et al.,2013. The mechanism of mesna in protection from cisplatin-induced ovarian damage in female rats. Journal of Gynecologic Oncology.24(2):177-85.
  46. Morgan, S., Anderson, R.A., Gourley,C., Wallace, W.H., Spears, N.,2012. How do chemotherapeutic agents damage the ovary? Human Reproduction update.18(5):525-35.
  47. Oktay, K., Schenken, R.S., Nelson, J.F., 1995.Proliferating cell nuclear antigen marks the initiation of follicular growth in the rat. Biology of Reproduction. 53(2):295-301.
  48. Omar, H.A., Mohamed, W.R., Arafa el, S.A., Shehata, B.A., El Sherbiny, G.A., Arab, H.H., et al.,2016. Hesperidin alleviates cisplatin-induced hepatotoxicity in rats without inhibiting its antitumor activity. Pharmacological Reports: PR. 68(2):349-56.
  49. Pandir, D., Kara, O., Kara, M.,2014. Protective effect of bilberry (Vaccinium myrtillus L.) on cisplatin induced ovarian damage in rat. Cytotechnology. 66(4):677-85.
  50. Parlakgumus, H.A., Aka, B. F., Bulgan, K. E., Simsek, E., Parlakgumus, A.,2014. Atorvastatin for ovarian torsion: effects on follicle counts, AMH, and VEGF expression. European journal of Obstetrics, Gynecology, and Reproductive Biology.175:186-90.
  51. Qian, G., Dai, L., Yu, T.,2019. Thioridazine Sensitizes Cisplatin Against Chemoresistant Human Lung and Ovary Cancer Cells. DNA and Cell Biology.38(7):718-24.
  52. Roness, H., Kalich-Philosoph, L., Meirow, D., 2014.Prevention of chemotherapy-induced ovarian damage: possible roles for hormonal and non-hormonal attenuating agents. Human Reproduction Update. 20(5):759-74.
  53. Rybak, L.P., Whitworth, C.A., Mukherjea, D., Ramkumar, V.,2007. Mechanisms of cisplatin-induced ototoxicity and prevention. Hearing research.226(1-2):157-67.
  54. Saribas, G.S., Erdogan, D., Goktas, G., Akyol, S.N., Hirfanoglu, I.M., Gurgen, S.G., et al,2016. Examining the protective effects of acetyl l-carnitine on cisplatin-induced uterine tube toxicity. Journal of obstetrics and gynaecology: the journal of the Institute of Obstetrics and Gynaecology.;36(8):1086-92.
  55. Sener, M.T., Sener, E., Tok, A., Polat, B., Cinar, I., Polat, H., et al.,2012. Biochemical and histologic study of lethal cisplatin nephrotoxicity prevention by mirtazapine. Pharmacological reports: PR.64(3):594-602.
  56. Siu, L.L., Moore, M.J.,1998. Use of mesna to prevent ifosfamide-induced urotoxicity. Supportive care in cancer: official journal of the Multinational Association of Supportive Care in Cancer. 6(2):144-54.
  57. Srivastava, A.N., Gupta, A., Srivastava, S., Natu, S.M., Mittal, B., Negi, M.P., et al.,2010. Cisplatin combination chemotherapy induces oxidative stress in advance non small cell lung cancer patients. Asian Pacific journal of Cancer Prevention: APJCP.11(2):465-71.
  58. Streuli, I., Fraisse, T., Pillet, C., Ibecheole, V., Bischof, P., de Ziegler, D.,2008. Serum antimullerian hormone levels remain stable throughout the menstrual cycle and after oral or vaginal administration of synthetic sex steroids. Fertility and Sterility.90(2):395-400.
  59. Stroud, J.S., Mutch, D., Rader, J., Powell, M., Thaker, P.H., Grigsby, P.W.,2009. Effects of cancer treatment on ovarian function. Fertility and Sterility. 92(2):417-27.
  60. Visser, J.A., de Jong, F.H., Laven, J.S., Themmen, A.P.,2006. Anti-Mullerian hormone: a new marker for ovarian function. Reproduction (Cambridge, England).131(1):1-9
  61. Weijl, N.I., Hopman, G.D., Wipkink-Bakker, A., Lentjes, E.G., Berger, H.M., Cleton, F.J., et al.,1998. Cisplatin combination chemotherapy induces a fall in plasma antioxidants of cancer patients. Annals of oncology: official journal of the European Society for Medical Oncology. 1998;9(12):1331-7.
  62. Wu, Y., Ma, C., Zhao, H., Zhou, Y., Chen, Z.2018. Alleviation of endoplasmic reticulum stress protects against cisplatin-induced ovarian damage.16(1):85. Xiao, S., Zhang, J., Liu,M., Iwahata, H., Rogers, H.B., Woodruff, T.K.,2017. Doxorubicin Has Dose-Dependent Toxicity on Mouse Ovarian Follicle Development, Hormone Secretion, and Oocyte Maturation. Toxicological Sciences: an Official Journal of the Society of Toxicology. 157(2):320-9.
  63. Yeh, J., Kim, B., Liang, Y.J., Peresie, J.,2006. Mullerian inhibiting substance as a novel biomarker of cisplatin-induced ovarian damage. Biochemical and Biophysical Research Communications. 348(2):337-44.
  64. Yeh, J., Kim, B.S., Peresie, J., 2008. Protection against cisplatin-induced ovarian damage by the antioxidant sodium 2-mercaptoethanesulfonate (mesna) in female rats. American Journal of Obstetrics and Gynecology. 198(4):463.e1-6; discussion.e6-7. Yeh, J., Kim, B.S., Peresie, J.,2008. Protection against cisplatin-induced ovarian damage by the antioxidant sodium 2-mercaptoethanesulfonate (mesna) in female rats. American journal of obstetrics and gynecology.198(4):463 e1-6; discussion e6-7. Ypsilantis, P., Tentes, I., Assimakopoulos, S.F., Kortsaris, A., Scopa, C.D., Simopoulos, C.,2004. Mesna ameliorates intestinal mucosa damage after ifosfamide administration in the rabbit at a dose-related manner. The Journal of surgical research. 121(1):84-91.