Effects of Rutin on Bladder Contractility and Histopathology in Cyclophosphamide-Induced Hemorrhagic Cystitis in Rats

Yıl 2018, Cilt: 13 Sayı: 3, 337 - 346, 25.12.2018

Volkan Gelen Emin Şengül Serkan Yıldırım Fikret Çelebi Ali Çınar

https://doi.org/10.17094/ataunivbd.370609

Cited By: 1

Öz

In this study, the effects of Rutin on the isolated urinary bladder smooth muscle contractions and bladder histopathology in Cyclophosphamide (CP)-induced hemorrhagic cystitis in rats were investigated. In study, twenty-four adult female Sprague Dawley rats were used and the avarage weight of the rats was 200-250 g. Four experimental groups were formed and each group had 6 rats. The control and CP groups were administrated intraperitoneally (ip) physiologic saline solution for 7 days. Also, CP group was injected the single dose of CP (150 mg/kg, ip) on the fifth day of saline administration. The Rutin application groups, Rutin (50 mg/kg, ip) dissolved in physiological saline were injected for 7 days. The Rutin+CP group was administered a single dose of CP on the fifth day of Rutin administration. On the 8th day of the experimental procedure, the rats were decapitated in the presence of anesthesia and their bladders were isolated. The contraction values induced by Acetylcholine (ACh) (10-4 M) and Potassium Chloride (KCI) (60 mM) in isolated bladder smooth muscle strips were obtained. Besides, urinary bladders were performed the histopathologic evaluation by staining with hematoxylin eosin. It was determined that the increased in vitro contractions induced by ACh and KCl in the CP group rats but not statistically significant (P>0.05) and Rutin administration was reduced the increased contraction responses. Histopathological examination was seen that Rutin reduced these changes while epithelial rash in the bladder lumen, desquamation in the mucosal epithelium, coagulation necrosis and severe erythrocyte. In conclusion, in CP-induced hemorrhagic cystitis was determined to be a protective effect of Rutin application on bladder contractility and histopathology.

Anahtar Kelimeler

Cyclophosphamide, Cystitis, Histopathology, Rat, Rutin

Ratlarda Cyclophosphamide ile İndüklenen Hemorajik Sistitte Mesane Kontraktilitesi ve Histopatolojisi Üzerine Rutin’in Etkileri

Öz

Bu çalışmada, ratlarda Cyclophosphamide (CP) ile indüklenen hemorajik sistitte izole mesane düz kas kontraksiyonları ve mesane histopatolojisi üzerine Rutin’in etkileri araştırıldı. Çalışmada 24 adet erişkin dişi Sprague Dawley rat kullanıldı ve ratların ağırlıkları ortalama 200-250 gramdı. Dört deney grubu oluşturuldu ve her bir grupta 6 rat vardı. Kontrol ve CP grubuna 7 gün intraperitoneal (ip) serum fizyolojik uygulandı. Ayrıca, CP grubuna serum fizyolojik uygulamasının 5. günü tek doz CP (150 mg/kg, ip) enjekte edildi. Rutin uygulanan gruplara serum fizyolojikte çözdürülmüş Rutin (50 mg/kg, ip) 7 gün enjekte edildi. Rutin+CP grubuna, Rutin uygulamasının 5. günü tek doz CP uygulandı. Deneysel uygulamanın 8. günü ratlar anestezi eşliğinde dekapite edilerek mesaneleri izole edildi. İzole mesane düz kas şeritlerinde Asetilkolin (Ach) (10-4 M) ve Potasyum Klorür (KCI) (60 mM) ile indüklenen kontraksiyon değerleri elde edildi. Ayrıca mesaneler hematoksilen eozin ile boyanarak histopatolojik değerlendirme yapıldı. CP grubundaki ratlarda ACh ve KCl ile indüklenen in vitro kontraksiyonların arttığı fakat istatistiksel önem arz etmediği (P>0.05) ve Rutin uygulamasının artan kontraksiyon cevaplarını azalttığı belirlendi. Histopatolojik incelemede mesane lümeninde epitel döküntü, mukoza epitelinde deskuamasyon, koagulasyon nekrozu ve şiddetli düzeyde eritrosit görülürken, Rutin’in bu değişiklikleri azalttığı görüldü. Sonuç olarak; CP ile indüklenen hemorajik sistitte mesane kontraktilitesi ve histopatolojisi üzerine Rutin uygulamasının protektif etkili olduğu belirlendi.

Anahtar Kelimeler

Cyclophosphamide, Histopatoloji, Rutin, Sistit, Rat

Kaynakça

• 1. Rashid S., Ali N., Nafees S., Hasan SK., Sultana S., 2014. Mitigation of 5-Fluorouracil induced renal toxicity by chrysin via targeting oxidative stress and apoptosis in wistar rats. Food Chem Toxicol, 66, 185-193.
• 2. Mahmoud AM., Hussein OE., Ramadan SA., 2013. Amelioration of cyclophosphamide-induced hepatotoxicity by the brown seaweed Turbenaria ornata. Int J Clin Pharmacol Toxicol, 11, 9-17.
• 3. Cuce G., Çetinkaya S., Koc T., Esen HH., Limandal C., Balcı T., Klakan S., Akoz M., 2015. Chemoprotective effect of vitamin E in cyclophosphamide-induced hepatotoxicity in rats. Chem Biol Interact, 232, 7-11.
• 4. Said E., Elkashef WF., Abdelaziz RR., 2015. Tranilast ameliorates cyclophosphamide-induced lung injury and nephrotoxicity. Can J Physiol Pharmacol, 944, 347-358.
• 5. Conklin DJ., Haberzettl P., Jagatheesan G., Baba S., Merchant ML., ProughR A., Williams JD., Sumanth DP., Bhatnagar A., 2015. Glutathione S-transferase P protects against cyclophosphamide-induced cardiotoxicity in mice. Toxicol Appl Pharmacol, 2852, 136-148.
• 6. Şengül E., Gelen V., Gedikli S., Özkanlar S., Gür C., Çelebi F., Çınar A., 2017. The protective effect of quercetin on cyclophosphamide-Induced lung toxicity in rats. Biomed Pharmacother, 92, 303-307.
• 7. Zanchi MM., Manfredini V., dos Santos Brum D., Vargas LM., Spiazzi CC., Soares MB., Izaguirry AP., Santos FW., 2015. Green tea infusion improves cyclophosphamide-induced damage on male mice reproductive system. Toxicol Rep, 2, 252-260.
• 8. Liu F., Li XL., Lin T., He DW., Wei GH., Liu JH., Li LS., 2012. The cyclophosphamide metabolite, acrolein, induces cytoskeleton changes and oxidative stress in sertoli cells. Mol Biol Rep, 39, 493-500.
• 9. Kim SH., Lee IC., Lim JH., Moon C., Bae CS., Kim SH., Shin DH., Park SC., Kim HC., Kim JC., 2012. Protective effects of pine bark extract on developmental toxicity of cyclophosphamide in rats, Food Chem Toxicol, 50, 109-115.
• 10. Levine LA., Richie JP., 1989. Urological complications of cyclophosphamide. J Urol, 141, 1063-1069.
• 11. Kim SH., Lee IC., Ko JW., Moon C., Kim SH., Shin IS., Seo YW., Kim HC., Kim JC., 2015. Diallyl disulfide prevents cyclophosphamide-induced hemorrhagic cystitis in rats through the inhibition of oxidative damage, MAPKs, and NF-κB pathways. Biomol Ther, 23, 180-188.
• 12. Kiuchi H., Takao T., Yamamoto K., Nakayama J., Miyagawa Y., Tsujimura A., Nonomura N., Okuyama A., 2009. Sesquiterpene lactone parthenolide ameliorates bladder inflammation and bladder overactivity in cyclophosphamide induced rat cystitis model by inhibiting nuclear factor-kappa B phosphorylation. J Urol, 18, 2339-2348.
• 13. Ahluwalia A., Maggi CA., Santicioli P., Lecci A., Giuliani S., 1994. Characterization of the capsaicin-sensitive component of cyclophosphamide-induced inflammation in the rat urinary bladder. Br J Pharmacol, 111, 1017-1022.
• 14. Giglio D., Ryberg AT., To K., Delbro DS., Tobin G., 2005. Altered muscarinic receptor subtype expression and functional responses in cyclophosphamide induced cystitis in rats. Auton Neurosci, 122, 9-20.
• 15. Jamshidzadeh A., Niknahad H., Azarpira N., Mohammadi-Bardbori A., Delnavaz M., 2015. Effect of lycopene on cyclophosphamide-induced hemorrhagic cystitis in rats. Iran J Med Sci, 341, 46-52.
• 16. Hollman PC., Katan MB., 1997. Absorption, metabolism and health effects of dietary flavonoids in man. Biomed Pharmacother, 51, 305-310.
• 17. Deng W., Fang X., Wu J., 1997. Flavonoids function as antioxidants: by scavenging reactive oxygen species or by chelating iron?. Radiat Phys Chem, 50, 271-276.
• 18. Aleksandrov PN., Speranskaia TV., Bobkov Iu G., Zagorevskii VA., Zykov DA., 1986. Effect of rutin and esculamine on models of aseptic inflammation. Farmakol Toksikol, 49, 84-86.
• 19. Deschner EE., Ruperto J., Wong G., Newmark HL., 1991. Quercetin and rutin as inhibitors of azoxymethanol-induced colonic neoplasia. Carcinogenesis, 12, 1193-1196.
• 20. Bear WL., Teel RW., 2000. Effects of citrus flavonoids on the mutagenicity of heterocyclic amines and on cytochrome P450 1A2 activity. Anticancer Res, 20, 3609-3614.
• 21. Chen S., Gong J., Liu F., Mohammed U., 2000. Naturally occurring polyphenolic antioxidants modulate IgE-mediated mast cell activation. Immunology, 100, 471-480.
• 22. Pozin VM., Skuratovskaia SG., Pocheptsova GA., 1996. Changes in the vascular Wall and ischemic damages to the myocardium in reversible episodes of heart muscle ischemia. Fiziologic Zhur, 42, 10-16.
• 23. Abarikwu SO., Otuechere CA., Ekor M., Monwuba K., Osobu D., 2012. Rutin ameliorates cyclophosphamide-induced reproductive toxicity in male rats. Toxicol Int, 19, 207.
• 24. Nafees S., Rashid S., Ali N., Hasan SK., Sultana S. 2015. Rutin ameliorates cyclophosphamide induced oxidative stress and inflammation in Wistar rats: role of NFκB/MAPK pathway. Chem Biol Interact, 231, 98-107.
• 25. Şengül E., Çelebi F., Gelen V., Çınar A., 2017. The Effects of Rosmarinus officinalis (Rosemary) aqueous extract on smooth muscle contractions in isolated rat urinary bladder. Atatürk Üniversitesi Vet Bil Derg, 12, 130-136.
• 26. Tripathi DN., Jena V., 2008. Astaxanthin inhibits cytotoxic and genotoxic effects of cyclophosphamide in mice germ cells. Toxicology, 248, 96-103.
• 27. Gelen V., Şengül E., Gedikli S., Atila G., Uslu H., Makav M., 2017. The protective effect of rutin and quercetin on 5-FU-induced hepatotoxicity in rats. Asian Pac J Trop Biomed, 7, 647-653.
• 28. Tong J., Mo QG., Ma BX., Ge LL., Zhou G., Wang YW., 2017. The protective effects of Cichorium glandulosum seed and cynarin against cyclophosphamide and its metabolite acrolein-induced hepatotoxicity in vivo and in vitro. Food Funct, 8, 209-219.
• 29. Mok MH., Knight GE., Andrews PL., Hoyle CH., Burnstock G., 2000. The effects of cyclophosphamide on neurotransmission in the urinary bladder of Suncus murinus, the house musk shrew. J Auton Nerv Syst, 80, 130-136.
• 30. Andersson MC., Tobin G., Giglio D., 2008. Cholinergic nitric oxide release from the urinary bladder mucosa in cyclophosphamide‐induced cystitis of the anaesthetized rat. Br J Pharmacol, 153, 1438-1444.
• 31. Vizzard MA., Erdman SL., de Groat WC., 1993. Localization of NADPH diaphorase in bladder afferent and postganglionic efferent neurons of the rat. J Auton Nerv Syst, 44, 85-90.
• 32. Masuda H., Ogawa T., Kihara K., Chancellor MB., de Groat WC.,Yoshimura N., 2007. Effects of anaesthesia on the nitrergic pathway during the micturition reflex in rats. BJU Int, 100, 175-180.
• 33. Andersson KE., Arner A., 2004. Urinary bladder contraction and relaxation: physiology and pathophysiology. Physiol Rev, 84, 935-986.
• 34. Gray KJ., Engelmann UH., Johnson EH., Fishman IJ., 1986. Evaluation of misoprostol cytoprotection of the bladder with cyclophosphamide (cytoxan) therapy. J Urol, 133, 497-500.
• 35. Ribeiro RA., Feritas HC., Campos MC., Santos CC., Figueiredo FC., Brito GA., Cunha FQ., 2002. Tumor necrosis factor-a and interleukin-1b mediate the production of nitric oxide involved in the pathogenesis of ifosfamide induced hemorrhagic cystitis in mice. J Urol, 67, 2229-2234.
• 36. Szabo C., 1996. The pathophysiological role of peroxynitrite in shock, inflammation, and ischemia-reperfusion injury. Shock, 6, 79-88.
• 37. Cuzzocrea S., Reiter RJ., 2001. Pharmacological action of melatonin in shock, inflammation, and ischemia/reperfusion injury. Eur J Pharmacol, 426, 1-10.
• 38. Korkmaz A., Oter S., Deveci S., Ozgurtas T., Topal T., Sadir S., Bilgic H., 2003. Involvement of nitric oxide and hyperbaric oxygen in the pathogenesis of cyclophosphamide induced hemorrhagic cystitis in rats. J Urol, 170, 2498-2502.
• 39. Souza-Fiho MV., Lima MV., Pompeu MM., Ballejo G., Cunha FQ., Ribeiro Rde A., 1997. Involvement of nitric oxide in the pathogenesis of cyclophosphamide-induced hemorrhagic cystitis. Am J Pathol, 150, 247-256.
• 40. Vieira MM., Macedo FY., Filho JN., Costa AC., Cunha AN., Silveira ER., Brito GA., Ribeiro RA., 2004. Ternatin, a flavonoid, prevents cyclophosphamide and ifosfamide-induced hemorrhagic cystitis in rats. Phytother Res, 18, 135-141.
• 41. Hanasaki Y., Ogawa S., Fukui S., 1994. The correlation between active oxygens scavenging and antioxidative effects of flavonoids. Free Radic Biol Med, 16, 845-850.
• 42. Ursini F., Maiorino M., Morazzoni P., Roveri A., Pifferi G., 1994 A novel antioxidant flavonoid (IdB 1031) affecting molecular mechanisms of cellular activation. Free Radic Biol Med, 16, 547-553.
• 43. Hozayen WG., 2012. Effect of hesperidin and rutin on doxorubicin induced testicular toxicity in male rats. Int J Food Nutr Sci, 1, 31-42.