2-MERCAPTOETAN SÜLFONAT (MESNA)’IN, PROTAMİN SÜLFATIN TETİKLEDİĞİ MESANE HASARI ÜZERİNDEKİ KORUYUCU ETKİLERİ

Abstract

Amaç: Bu morfolojik ve biyokimyasal çalışmanın amacı 2-mercaptoetan sulfonat (MESNA)’ın protamin sülfat (PS)’ ın tetiklediği mesane hasarı üzerindeki koruyucu etkilerinin araştırılmasıdır. Gereç ve Yöntem: Wistar albino dişi sıçanlar kateterize edilerek mesane içine fosfat tamponu (kontrol grubu) ya da fosfat tamponu içinde çözünmüş PS (PS grubu) infüze edildi. PS + MESNA grubundaki sıçanlara PS verilmesinden sonra, 3 gün boyunca, 50 mg/kg MESNA i.p. olarak enjekte edildi. Mesane morfolojleri ışık ve taramalı elektron mikroskopi düzeylerinde incelendi; ayrıca dokudaki malondialdehit ve glutatyon düzeylerine de bakıldı. Bulgular: PS grubunda ülserli alanlar, düzensiz mukus tabakası, inflamatuvar hücre infiltrasyonu ve mast hücre sayısında artış gözlendi. PS + MESNA grubunda PS grubuna oranla, normal ürotel görüntüsü ve glikozaminoglikan tabakası ile inflamatuvar hücrelerin ve mukozal mast hücrelerinin sayısında azalma izlendi. PS’ nin tetiklemesi ile oluşan hasarda önemli rol oynayabilecek olan serbest radikallerin ortaya çıkması sonucunda malondialdehit düzeyi artmış glutatyon düzeyi ise düşmüş bulundu. PS + MESNA grubunda morfolojik bulgularla uyumlu olarak, malondialdehit düzeyi önemli derecede düşmüş, glutatyon düzeyi ise artmıştır. Sonuç: Bu bulgular, mesane mukozasında PS’ ın tetiklediği morfolojik hasar ve biyokimyasal değişikliklerin MESNA tedavisi ile önemli düzeyde önlenebileceğini göstermektedir.

Keywords

• MESNA, Protamin sülfat, Mesane

References

1. 1. Horrow JC. Protamine a review of its toxicity. Anesth Analg 1985;64:348-361.
2. 2. Peterson MW, Gruenhaupt D. Protamine interaction with the epithelial cell surface. J Appl Physiol 1992;72: 236-241.
3. 3. Quinton PM, Philpott CW. A role for anionic sites in epithelial architecture. J Cell Biol 1973;56:787-796.
4. 4. Tzan CJ, Berg J, Lewis SA. Effect of protamine sulfate on the permeability properties of the mammalian bladder. J Membrane Biol 1993;133:227-242.
5. 5. Niku DS, Stein PC, Scherz HC, Parsons CL. A new method for cytodestruction of bladder epithelium using protamine sulfate and urea. J Urol 1994;152:1025-1028.
6. 6. Johansson SL, Fall M. Pathology of interstitial cystitis. Urol Clin North Am 1994; 21: 55-62.
7. 7. Fall M, Johansson SL, Vahlne A. A clinicopathological and virological study of interstitial cystitis. J Urol 1985;133:771-773.
8. 8. Sant GR. Diagnosis of interstitial cystitis. A clinical, endoscopic and pathologic approach. In: Hanno PM, Staskan DR, Krane RJ, Wein AJ..Interstitial Cystitis. London.: Springer. 1990: 107.

9. 9. Fowler JE, Jr Lynes WL, Lau JLT, Ghosh L, Mounzer A. Interstitial cystitis is associated with intraurethelial Tamm-Horsfall protein. J Urol 1988;140:1385-1389.
10. 10. Gillenwater JY, Wein AJ. Summary of the National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases Workshop on Interstitial Cystitis, National Institutes of Health, Bethesda, Maryland, August 28-29, 1987. J Urol 1988;140 :203-206.
11. 11. Gressier B, Lebegue S, Brunet C, et al: Pro-oxidant properties of methotrexate: evaluation and prevention by anti-oxidant drug. Pharmazie 1994;49:679–681.
12. 12. Gressier B, Lebegue N, Brunet C, et al. Scavenging of reactive oxygen species by letosteine, a molecule with two blocked-SH groups. omparison with free –SH drugs. Pharm World Sci 1995;17:76–80.
13. 13. Goren MP, McKenna LM, Goodman TL. Combined intravenous and oral mesna in outpatients treated with ifosfamide. Cancer Chemother Pharmacol 2003; 40:371–375.
14. 14. Kurovski V, Wagner T. Urinary excretion of ifosfamide, 4-hydroxyfosfamide, 3- and 2-dechloroethylifosfamide, mesna, and dimesna in patients on fractionated intravenous ifosfamide and concomitant mesna therapy. Cancer Chemother Pharmacol 1997;39:431–439.
15. 15. Berrigan MJ, Marinello AJ, Pavelic Z, Williams CJ, Struck RF, Gurtoo HL.Protective role of thiols in cyclophosphamide-induced urotoxicity and depression of hepatic drug metabolism. Cancer Res 1982;42:3688– 3695.
16. 16. West NJ. Prevention and treatment of hemorrhagic cystitis. Pharmacother 1997; 17:696–706.
17. 17. Nishikawa A, Morse MA, Chung FL. Inhibitory effects of 2-mercaptoethane sulfonate and 6-phenylhexyl isothiocyanate on urinary bladder tumorigenesis in rats induced by N-butyl-N-(4-hydroxybutyl) nitrosamine. Cancer Lett 2003;193:11–16.
18. 18. Umemura T, Hasegawa R, Sai-Kato K, et al. Prevention by 2-mercaptoethane sulfonate and N-acetylcysteine of renal oxidative damage in rats treated with ferric nitrilotriacetate. Jpn J Cancer Res 1996;87:882–886.
19. 19. Beuge JA, Aust SD. Microsomal lipid peroxidation. Method Enzymol 1978;52:302–311.
20. 20. Beutler E. Glutathione in red blood cell metabolism. A manual of Biochemical Methods. Published by Grune and Stratton. New York, 1975: 112–114.
21. 21. Lilly JD, Parsons L. Bladder surface glycosaminoglycans. Is a human epithelial permeability barrier?. Surg. Gynecol Obstet 1990;171:493-496.
22. 22. Parsons CL, Lilly JD, Stein P. Epithelial dysfunction in nonbacterial cystitis (interstitial cystitis). J Urol 1991;145:732-735.
23. 23. Parsons CL, Housley T, Schmidt JD, Lebow D. Treatment of interstitial cystitis with intravesical heparin. Br J Urol 1994;73:504-507.
24. 24. Parsons CL, Boychuk D, Jones S, Hurst R, Callahan H. Bladder surface glycosaminoglycans: An epithelial permeability barrier. J Urol 1990;143:139-142.
25. 25. Anderström CRK, Fall M, Johansson SL. Scanning electron microscopic findings in interstitial cystitis. Br J Urol 1989;63:270-275.
26. 26. Skinner R, Sharkey IM., Pearson ADJ, Craft AW. Ifosfamide, mesna, and nephrotoxicity in children. J Clin Oncol 1993;11:173–190.
27. 27. Lord-Fontaine S, Averill DA. Enhancement of cytotoxicity of hydrogen peroxide by hyperthermia in Chinese hamster ovary cells: role of antioxidant defenses. Arch Biochem Biophys 1999;363:283–295.
28. 28. Souid AK, Fahey RC, Aktas MK, et al. Blood thiols following amifostine and mesna infusions, a pediatric oncology group study. Drug Metab Dispos 2001;29:1460–1466.
29. 29. Garcia JJ, Reiter RJ, Guerrero JM, Escames G, Yu BP, Oh CS, Munoz-Hoyos A. Melatonin prevents changes in microsomal membrane fluidity during induced lipid peroxidation. FEBS Lett 1997:408:297–300.
30. 30. Ross D. Glutathione, free radicals and chemotherapeutic agents. Mechanisms of free-radical induced toxicity and glutathione-dependent protection. Pharmacol Ther 1988;37:231–249.
31. 31. Kabasakal L, Sehirli AO, Cetinel S, Cikler E, Gedik N, Sener G. Mesna (2-mercaptoethane sulfonate) prevents ischemia/reperfusion induced renal oxidative damage in rats. Life Sci 2004,Sep 24;75:2329-2340.
32. 32. Vieira MM, Macedo FY, Filho JN, et al.. Ternatin, a flavonoid, prevents cyclophosphamide and ifosfamideinduced hemorrhagic cystitis in rats. Phytother Res 2004 Feb;18:135-141.
33. 33. Granger DN, Korthuis RJ. Physiological mechanisms of postischemic tissue injury. Annu Rev Physiol. 1995;57:311–332.
34. 34. Zimmerman BJ, Grisham MB, Granger DN: Role of oxidants in ischemia-reperfusion induced granulocyte infiltration. Am J Physiol 1990;258:G185–G190.
35. 35. Theoharides TC, Kempuraj D, Sant GR. Mast cell involvement in interstitial cystitis: a review of human and experimental evidence. Urology 2001;57 (suppl.6A):47-55.