Effects of Rutin on 5-Fluorouracil-Induced Nephrotoxicity in Rats

Year 2021, Volume: 16 Issue: 3, 243 - 250, 30.12.2021

Samet Tekin , Fikret Çelebi

https://doi.org/10.17094/ataunivbd.930228

Cited By: 1

Abstract

5-Fluorouracil (5-FU) is a widely used agent in chemotherapy. This study was aimed to investigate the effects of Rutin on 5-FU-induced nephrotoxicity in rats. In our study, 40 male adult rats were used and the rats were divided into five groups as Control, 5-FU, Rutin50+5-FU, Rutin100+5-FU, and Rutin100. According to the experimental protocol, rats were administered 50 and 100 mg/kg doses of Rutin and a single dose (200 mg/kg) of 5-FU for 14 days. On the 15th day of the experimental study, intracardiac blood samples were taken from rats under anesthesia, and rats were decapitated to obtain kidney tissue samples. Urea, creatinine, and blood urea nitrogen (BUN) values in serum samples were analyzed in an autoanalyzer. Kidney tissues were detected in 10% formalin and hematoxylin-eosin (HE) staining was performed. Histopathological examination was performed to determine the effects of 5-FU and Rutin application on kidney tissue. In the 5-FU group; serum urea, creatinine and BUN levels increased significantly compared to other groups. It was observed that an especially high dose of Rutin prevented 5-FU-induced increases in kidney function tests and histopathological changes caused by 5-FU in kidney tissue. In consequence of this study, it was determined that Rutin significantly prevented 5-FU-induced kidney toxicity in rats.

Keywords

5-Fluorouracil, Nephrotoxicity, Rat, Rutin

Sıçanlarda 5-Florourasil ile İndüklenen Nefrotoksisitede Rutin’in Etkileri

Abstract

5-Florourasil (5-FU) kemoterapide yaygın olarak kullanılan bir ajandır. Bu çalışmada, sıçanlarda 5-FU ile indüklenen nefrotoksisitede Rutin’in etkilerinin araştırılması amaçlandı. Çalışmamızda 40 adet erkek erişkin sıçan kullanıldı ve sıçanlar Kontrol, 5-FU, Rutin50+5-FU, Rutin100+5-FU ve Rutin100 olmak üzere beş gruba ayrıldı. Deneysel protokole göre sıçanlara, 14 gün boyunca Rutin’in 50 ve 100 mg/kg dozları ve tek doz (200 mg/kg) 5-FU uygulandı. Deneysel çalışmanın 15. gününde sıçanlardan anestezi altında intrakardiyak kan örnekleri alındı ve böbrek doku örneklerinin alınması için sıçanlar dekapite edildi. Serum örneklerinde üre, kreatinin ve kan üre nitrojen (BUN) değerleri otoanalizörde analiz edildi. Böbrek dokuları %10’luk formalinde tespit edildi ve hematoksilen-eozin (HE) boyaması yapıldı. Böbrek dokusunda 5-FU ve Rutin uygulamasının etkilerinin belirlenmesi amacıyla histopatolojik inceleme yapıldı. 5-FU grubunda; serum üre, kreatinin ve BUN seviyeleri diğer gruplara göre anlamlı düzeyde arttı. Rutin’in özellikle yüksek dozu, böbrek fonksiyon testlerinde 5-FU kaynaklı artışları ve 5- FU’nun böbrek dokusunda meydana getirmiş olduğu histopatolojik değişiklikleri önlediği görüldü. Bu çalışmanın sonucunda, Rutin’in sıçanlarda 5-FU ile indüklenen böbrek toksisitesini önemli ölçüde önlediği belirlendi.

Keywords

5-Florourasil, nefrotoksisite, rutin, Sıçan

References

• 1. 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.
• 2. Gelen V., Şengül E., Çınar DA., 2021. The effects of rutin and quercetin on ECG parameters in 5-FU-induced cardiotoxicity rat model. WJARR, 9, 253-257.
• 3. Gedikli S., Şengül E., 2019. Ratlarda siklofosfamid ile indüklenen hepatotoksisite üzerine kuersetinin etkileri. Dicle Tıp Derg, 46, 41-50.
• 4. Çelebi F., Cengiz İ., Çinar A., Şengül E., 2020. Protective effects of Naringin on free radicals and antioxidants in cyclophosphamide induced rats. Atatürk Üniversitesi Vet Bil Derg, 15, 231-236.
• 5. Gelen V., Şengül E., 2020. Antioxidant, anti-inflammatory and antiapoptotic effects of Naringin on cardiac damage induced by cisplatin. Indian j tradit knowl, 19, 459-465.
• 6. Çelebi F., Cengiz İ., Cinar A., Şengül E., 2020. Siklofosfamidle İndüklenmiş Ratlarda Serbest Radikaller ve Antioksidanlar Üzerine Naringinin Protektif Etkileri. Atatürk Üniversitesi Vet Bil Derg, 15, 231-236.
• 7. Yıldırım S., 2017. Investigation by histopathological and TUNEL method of the protective effect of Resveratrol on carbon tetrachloride induced liver toxicity in rats. Atatürk Üniversitesi Vet Bil Derg, 12, 178-186.
• 8. Yildirim S., Celikezen FC., Oto G., Sengul E., Bulduk M., Tasdemir M., Cinar DA., 2018. An investigation of protective effects of litium borate on blood and histopathological parameters in acute cadmium-induced rats. Biol Trace Elem Res, 182, 287-294.
• 9. Comba B., Çınar A., Comba A., Gencer YG., 2016. Sıçanlarda ACTH uygulamasının böbrek fonksiyon testleri, elektrolitler ve hematolojik parametreler üzerine etkileri. Ankara Üniv Vet Fak Derg, 63, 229-233.
• 10. Yildirim S., Ekin S., Huyut Z., Oto G., Comba A., Uyar H., Cinarf A., 2018. Effect of chronic exposure to sodium fluoride and 7, 12-dimethylbenz [a] anthracene on some blood parameters and hepatic, renal, and cardiac histopathology in rats. Fluoride, 51, 274-286.
• 11. Perazella MA., Izzedine H., 2015. New drug toxicities in the onco-nephrology world. Kidney Int, 87, 909-917.
• 12. Al-Asmari AK., Al-Zahrani AM., Khan AQ., Al-Shahrani HM., Ali Al Amri M., 2016. Taurine ameliorates 5-flourouracil-induced intestinal mucositis, hepatorenal and reproductive organ damage in Wistar rats: A biochemical and histological study. Hum Exp Toxicol, 35, 10-20.
• 13. Gelen V., Şengül E., Yıldırım S., Atila G., 2018. The protective effects of naringin against 5-fluorouracil-induced hepatotoxicity and nephrotoxicity in rats. Iran J Basic Med Sci, 21, 404.
• 14. Yousef HN., Aboelwafa HR., 2017. The potential protective role of taurine against 5-fluorouracil-induced nephrotoxicity in adult male rats. Exp Toxicol Pathol, 69, 265-274.
• 15. 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, 66, 185-193.
• 16. Yildirim S., Çelikezen FÇ., Belhan S., Oto G., Eser G., Şengül E., Cinar D., 2020. Investigation of protective effects of lithium borate on spermatogenesis and testes histopathology against cadmium-induced acute toxicity in rats. Turk J Zool, 44, 291-301.
• 17. Yildirim S., Ozkan C., Huyut Z., Çınar A., 2019. Detection of Se, vit. E, vit. A, MDA, 8-OHdG, and CoQ10 levels and histopathological changes in heart tissue in sheep with white muscle disease. Biol Trace Elem Res, 188, 419-423.
• 18. Manach C., Morand C., Demigne C., Texier O., Regerat F., Remesy C., 1997. Bioavailability of rutin and quercetin in rats. FEBS Lett, 409, 12-16.
• 19. La Casa C., Villegas I., De La Lastra CA., Motilva V., Calero MM., 2000. Evidence for protective and antioxidant properties of rutin, a natural flavone, against ethanol induced gastric lesions. J Ethnopharmacol, 71, 45-53.
• 20. Selloum L., Bouriche H., Tigrine C., Boudoukha C., 2003. Anti-inflammatory effect of rutin on rat paw oedema, and on neutrophils chemotaxis and degranulation. Exp Toxicol Pathol, 54, 313-318.
• 21. Punithavathi VR., Shanmugapriya K., Prince PSM., 2010. Protective effects of rutin on mitochondrial damage in isoproterenol-induced cardiotoxic rats: an in vivo and in vitro study. Cardiovasc Toxicol, 10, 181-189.
• 22. Chen SS., Gong J., Liu FT., Mohammed U., 2000. Naturally occurring polyphenolic antioxidants modulate IgE‐mediated mast cell activation. Immunology, 100, 471-480.
• 23. Sengul E., Gelen V., Gedikli S., 2021. Cardioprotective activities of quercetin and rutin in sprague dawley rats treated with 5-fluorouracil. J Anim Plant Sci, 31, 423-431.
• 24. Gelen V., Șengül E., Yıldırım S., Celebi F., Cınar A., 2018. Effects of Rutin on bladder contractility and histopathology in cyclophosphamide-induced hemorrhagic cystitis in rats. Atatürk Üniversitesi Vet Bil Derg, 13, 337-346.
• 25. 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, 92, 303-307.
• 26. Bülbül GY., Mis L., Șengül E., Yıldırım S., Çelebi F., Çinar A., 2018. Protective effects of Naringin on liver enzymes (AST, ALT, ALP) and histopathology in Cyclophosphamide-induced rats. Atatürk Üniversitesi Vet Bil Derg, 13, 182-190.
• 27. Dağ Y., Şengül E., Selçuk M., Yıldırım S., Çelebi F., Çınar A., 2018. Ratlarda Cyclophosphamide ile indüklenen nefrotoksisitede bazı hematolojik parametreler ve böbreğin histopatolojisi üzerine naringinin protektif etkileri. Atatürk Üniversitesi Vet Bil Derg, 13, 219-228.
• 28. Sengul E., Gelen SU., Yıldırım S., Çelebi F., Çınar A., 2019. Probiotic bacteria attenuates cisplatin-induced nephrotoxicity through modulation of oxidative stress, inflammation and apoptosis in rats. Asian Pac J Trop Biomed, 9, 116.
• 29. Sengul E., Gelen V., Yildirim S., Tekin S., Dag Y., 2021. The effects of selenium in acrylamide-induced nephrotoxicity in rats: roles of oxidative stress, inflammation, apoptosis, and DNA damage. Biol Trace Elem Res, 199, 173-184.
• 30. Gelen V., Şengül E., Yıldırım S., Senturk E., Tekin S., Kükürt A., 2021. The protective effects of hesperidin and curcumin on 5-fluorouracil–induced nephrotoxicity in mice. Environ Sci Pollut Res Int, 28, 47046-47055.
• 31. Gelen V., Şengül E., 2021. Protective effects of resveratrol on kidney function tests and renal histopathology in carbon tetrachloride-induced renal toxicity in rats. WJARR, 10, 156-161.
• 32. Salazar JH., 2014. Overview of urea and creatinine. Lab Med, 45, e19-e20.
• 33. Ikemura K., Oshima K., Enokiya T., Okamoto A., Oda H., Mizuno T., Okuda M., 2017. Co-administration of proton pump inhibitors ameliorates nephrotoxicity in patients receiving chemotherapy with cisplatin and fluorouracil: a retrospective cohort study. Cancer Chemother. Pharmacol, 79, 943-949.
• 34. Adikwu E., Biradee I., Ogungbaike TO., 2019. Therapeutic benefit of resveratrol in 5-fluorouracil-induced nephrotoxicity in rats. Biomed Res J, 6, 72.
• 35. Badawoud MH., Elshal EB., Zaki AI., Amin HA., 2017. The possible protective effect of L-arginine against 5-fluorouracil-induced nephrotoxicity in male albino rats. Folia Morphol, 76, 608-619.