Sisplatinin Neden Olduğu Nefrotoksisite Ve Ultrastrüktürel Hasar Üzerine Kurkuminin Koruyucu Etkisi

Year 2021, Volume: 8 Issue: 4, 598 - 605, 31.12.2021

Hülya Birinci Büşra Şen Halıcıoğlu Mustafa Öztatlıcı Mehmet Yüncü

https://doi.org/10.34087/cbusbed.881099

Cited By: 1

Abstract

Giriş ve Amaç: Antineoplastik bir ajan olan sisplatinin önemli yan etkilerinden biri de nefrotoksisitedir. Sisplatin böbrek genel yapısının bozulmasına ve fonksiyon kaybına sebep olur. Böbrekte glomerüler filtrasyonun düşmesine, serum kreatininin yükselmesine, serum potasyum ve magnezyum seviyelerinin düşmesine ve iskemik-nekrotik hasara yol açmaktadır. Kurkuminin, antioksidan, antifibrojenik, antikanserojenik ve antiinflamatuvar özellikleri vardır. Bu çalışmada, sıçanlarda, sisplatinin böbreklerde yaptığı hasara karşı kurkuminin koruyucu etkisinin araştırılması amaçlandı.
Gereç ve Yöntemler: Wistar albino cinsi 26 erişkin sıçan 4 gruba ayrıldı. Kontrol grubuna 6 gün boyunca DMSO intraperitoneal (i.p.) olarak verildi. Sisplatin grubuna 3. gün 20 mg/kg sisplatin i.p. olarak tek doz uygulandı. Kurkumin grubuna 6 gün boyunca günde 200 mg/kg kurkumin i.p. olarak verildi. Sisplatin +kurkumin grubuna 6 gün boyunca günde 200 mg/kg kurkumin ve 3. gün tek doz 20 mg/kg sisplatin i.p. olarak verildi. Sıçanlar 7. gün sakrifiye edildi. Alınan böbrek dokularında ışık ve elektron mikroskopik değerlendirmelerin yanı sıra biyokimyasal analizler yapıldı.
Bulgular: Yalnızca kurkumin verdiğimiz grupta herhangi bir hasar yoktu ve kontrol grubundakilere benzerdi. Sisplatin verilen grupta ise renal kortekste konjesyon, intraselüler kastlar ve tübüler nekroz izlendi. Ancak kurkumin+sisplatin grubunda bu hasarlar azaldı ve dokudaki genel hücre organizasyonunun normale yakın olduğu gözlendi.
Sonuç: Sisplatinin neden olduğu nefrotoksisiteye karşı kurkuminin koruyucu bir ajan olabileceği önerilmektedir.

Keywords

böbrek, elektron mikroskobu, kurkumin, nefrotoksisite, sisplatin

Supporting Institution

Gaziantep Üniversitesi Bilimsel Araştırma Projeleri

Project Number

T.F.YLT.16.05

Thanks

Elektron mikroskop çalışmalarındaki katkılarından dolayı Çukurova Üniversitesi Tıbbi Histoloji-Embriyoloji Anabilim Dalı Başkanı Sayın Prof. Dr. Sait Polat başta olmak üzere tüm öğretim üyelerine teşekkür ederiz.

The Protective Effect of Curcumin on Nephrotoxicity and Ultrastructural Damage Induced by Cisplatin

Abstract

Objective: Nephrotoxicity is one of the important side effect of cisplatin which is an antineoplastic agent. It involves decreased glomerular filtration rate, high serum creatinin, lower serum potassium and magnesium levels and ischemic-necrotic damage on kidney. This situation causes degeneration of the general organ structure and loss of function. Curcumin is a compound that has primarily antioxidant, antifibrogenic, anticarsinogenic and antiinflammatory properties. In this study, it’s aimed to investigate the recuperative effect of curcumin against cisplatin-caused kidney damage in rats.
Materials and Methods: Wistar albino 26 Adult rats were divided into four groups. Control group received DMSO for six days via intraperitoneally. A single dose of 20 mg/kg cisplatin is intraperitoneally injected to cisplatin group on the third day of experiment. The curcumin+cisplatin group received intraperitoneal 200 mg/kg curcumin for six days and 20 mg/kg cisplatin on the third day. The curcumin group received 200 mg/kg curcumin for six days. The rats were sacrified at the seventh day. The kidney tissues were taken and necessary procedures were applied for light and electron microscopic evaluations and biochemical assays.
Results: There was no damage in the curcumin group and the results of this group was similar to the normal group. In the cisplatin group, we had showed congestion, intracellular casts and tubular necrosis in renal cortex. However, in the cisplatin+curcumin group, degenerative alterations decreased and general cell organisation of renal tissue was close to the normal group.
Conclusion: It has been suggested that curcumin may be a protective agent against cisplatin-induced nephrotoxicity.

Keywords

Cisplatin, Curcumin, Electron microscope, Kidney, Nephrotoxicity

Project Number

T.F.YLT.16.05

References

• Chirino, Y.I, Pedraza-Chaverri, J, Role of oxidative and nitrosative stress in cisplatin-induced nephrotoxicity, Experimental and Toxicologic Pathology, 2009, 61(3), 223-242.
• Palipoch, S, Punsawad, C, Koomhin, P, Suwannalert, P, Hepatoprotective effect of curcumin and alpha-tocopherol against cisplatin-induced oxidative stress, BMC complementary and alternative medicine, 2014, 14(1), 111.
• Pezeshki, Z, Khosravi, A, Nekuei, M, Khoshnood, S, Zandi, E, Eslamian, M, Talebi, A, Emami, SNED, Nematbakhsh, M. Time course of cisplatin-induced nephrotoxicity and hepatotoxicity, J Nephropathol, 2017, 6, 163–167.
• Amirshahrokhi, K, Khalili, A.R, Thalidomide ameliorates cisplatininduced nephrotoxicity by inhibiting renal inflammation in an experimental model, Inflammation, 2015, 38, 476–484.
• Pabla, N, Dong, Z, Cisplatin nephrotoxicity: mechanisms and renoprotective strategies, Kidney international, 2008, 73(9), p. 994-1007.
• dos Santos, N.A.G, Rodrigues, M.A.C, Martins, N.M, dos Santos, A.C, Cisplatin-induced nephrotoxicity and targets of nephroprotection: an update, Archives of toxicology, 2012, 86(8), 1233-1250.
• Peres, L.A.B, Cunha Júnior, A.D.D, Acute nephrotoxicity of cisplatin: molecular mechanisms, Jornal Brasileiro de Nefrologia, 2013, 35(4), 332-340.
• Li, C.Z, Jin, H.H, Sun, H.X, Zhang, Z.Z, Zheng, J.X, Li, S.H, Han, S.H, Eriodictyol attenuates cisplatin-induced kidney injury by inhibiting oxidative stress and inflammation, Eur J Pharmacol, 2016, 772, 124–130.
• Ognjanović, B.I, Djordjević, N.Z, Matić, M.M, Obradović, J.M, Mladenović, J.M, Štajn, A.Š, Saičić, Z.S, Lipid peroxidative damage on cisplatin exposure and alterations in antioxidant defense system in rat kidneys: a possible protective effect of selenium, Int J Mol Sci, 2012, 13, 1790–1803.
• Hosohata, K, Role of oxidative stress in drug-induced kidney injury, International journal of molecular sciences, 2016, 17(11), 1826.
• Rivera-Espinoza, Y, Muriel, P, Pharmacological actions of curcumin in liver diseases or damage, Liver International, 2009, 29, 10, 1457-1466.
• Aggarwal, B.B, Kumar, A, Bharti, A.C, Anticancer Potential of Curcumin: Preclinical and Clinical Studies, Antıcancer Research, 2003, 23, 363-398.
• Ahmed, A.Y, Gad, A.M, El-Raouf, O.M.A, Curcumin ameliorates diclofenac sodium-induced nephrotoxicity in male albino rats, J Biochem Mol Toxicol, 2017, 31, e21951.
• Pulido-Moran, M, Moreno-Fernandez, J, Ramirez-Tortosa, C, et al., Curcumin and health, Molecules, 2016, 21(3), 264.
• Sankar, P, Telang, A.G, Manimaran, A, Protective effect of curcumin on cypermethrin-induced oxidative stress in Wistar rats, Experimental and Toxicologic Pathology, 2012, 64(5), 487-493.
• Trujillo, J, Chirino, Y.I, Molina-Jijón, E, Andérica-Romero, A.C, Tapia, E, Pedraza-Chaverrí, J, Renoprotective effect of the antioxidant curcumin: Recent findings, Redox biology, 2013, 1(1), 448-456.
• Coca, S.G, Singanamala, S, Parikh, C.R, Chronic kidney disease after acute kidney injury: a systematic review and meta-analysis, Kidney international, 2012, 81(5), 442-448.
• Giordano, A, Tommonaro, G, Curcumin and cancer, Nutrients, 2019, 11(10), 2376.
• Farombi, E. O, Ekor, M, Curcumin attenuates gentamicin-induced renal oxidative damage in rats, Food and chemical Toxicology, 2006, 44(9), 1443-1448.
• Abdelrahman, A.M, Al Salam, S, AlMahruqi, A.S, Al husseni, I.S, Mansour, M.A, Ali, B.H, Nacetylcysteine improves renal hemodynamics in rats with cisplatin-induced nephrotoxicity, J Appl Toxicol, 2010, 30(1), 15-21.
• Atasayar, S, Gürer-Orhan, H, Orhan, H, Gürel, B, Girgin, G, Ozgüneş, H, Preventive effect of aminoguanidine compared to vitamin E and C on cisplatin-induced nephrotoxicity in rats, Exp Toxicol Pathol, 2009, 61(1), 23-32.
• Maliakel, D.M, Kagiya, T.V, Nair, C.K, Prevention of cisplatin-induced nephrotoxicity by glucosides of ascorbic acid and alpha- tocopherol, Exp Toxicol Pathol, 2008, 60(6), 521-7.
• Jariyawat, S, Kigpituck, P, Suksen, K, Chuncharunee, A, Chaovanalikit, A, Piyachaturawat, P, Protection against cisplatin-induced nephrotoxicity in mice by cyrcuma cumosa roxhb. ethanol extract, J Nat Med, 2009, 63(4), 430-436.
• Çetin, R, Devrim, E, Kılıçoğlu, B, Avcı, A, Çandır, Ö, Durak, İ, Cisplatin impairs antioxidant system and causes oxidation in rat kidney tissues: possible protective roles of natural antioxidant foods, Journal of Applied Toxicology, 2006, 26(1), 42-46.
• Mercantepe, F, Mercantepe, T, Topcu, A, Yılmaz, A, Tumkaya, L, Protective effects of amifostine, curcumin, and melatonin against cisplatin-induced acute kidney injury, Naunyn-Schmiedeberg's archives of pharmacology, 2018, 391(9), 915-931.
• Karakoc, H.T, Altintas, R, Parlakpinar, H, Polat, A, Samdanci, E, Sagir, M, Duran, Z.R, Protective Effects of Molsidomine Against Cisplatin-Induced Nephrotoxicity, Advances in clinical and experimental medicine: official organ Wroclaw Medical University, 2014, 24(4), 585-593.
• Tirkey, N, Kaur, G, Vij, G, Chopra, K, Curcumin, a diferuloylmethane, attenuates cyclosporine-induced renal dysfunction and oxidative stress in rat kidneys, BMC pharmacology, 2005, 5(1), 15.