Nursah BASOL, Oytun ERBAS, Ayfer MERAL, Aslı Yasemen SAVAS

Güçlü antikosidan kurkuminin sisplatinin neden olduğu karaciğer ve böbrek hasarında önemli etkileri

Amaç: Sisplatin (CIS) sıklıkla kullanılan oldukça güçlü bir anti kanser ajandır. Sisplatinin toksik etkileri kullanımını sınırlandırmaktadır. Sunulan bu deneysel çalışmada, sisplatinin nefrotoksik ve hepatotoksik yan etkilerine karşı kurkuminin (CUR) etkilerinin incelenmesi amaçlanmıştır.Yöntem: Sıçanlar her biri 7'şerli toplam 3 gruba ayrıldı. İlk grup, control grubu olarak, ikinci grup CIS (6 mg/kg, i.p)+ salin grubu ve 3. grup CIS (6 mg/kg, i.p) + CUR (100 mg/kg i.p) olarak belirlendi. Sisplatin tek doz olarak ve kurkumin ise 3 gün boyunca sıçanlara verildi. 3 gün sonra, karaciğer ve böbrek dokuları ve kan örnekleri histopatolojik ve biyokimyasal tekniklerle analiz edildi. Bulgular: Sisplatin+ kurkumin gurubunda BUN ve ALT değerleri sadece sisplatin uygulanan gruba göre daha düşük bulundu. Bunun yanında, SOD ve GSH düzeyleri sadece sisplatin verilen grupta CIS+CUR grubuna göre daha yüksekti. Karaciğer ve böbrek dokusunda histopatolojik olarak kurkuminin yararlı etkileri gözlendi. Sonuç: Sisplatin böbrek ve karaciğer dokuları üzerinde güçlü bir toksik etkiye sahiptir. Sunulan bu çalışma; kurkuminin, nefrotoksik ve hepatotoksik yan etkileri iyileştirmede önemli bir etkisi olduğunu öne sürmektedir.

The valuable effects of potent antioxidant curcumin in cisplatin induced liver and kidney injury

Objective: Cisplatin (CIS) is a potent anticancer drug that uses commonly. The toxic effects of CIS limit its usage. In the present experimental study, it is aimed to evaluate effects of curcumin (CUR) on CIS induced hepatotoxicity and nephrotoxicity. Method: The rats were separated into three groups as each composed of 7 rats. First one is control group, the second is the CIS (6 mg/kg, i.p) + saline group, and third is the CIS (6 mg/kg, i.p) + CUR (100 mg/kg i.p) group. CIS was given at single dose and CUR was given for 3 days. After 3 days, kidney, liver and blood samples were analyzed with histopathological and biochemical technics. Results: In CIS+ CUR group, there was decline in levels of Blood urea nitrogen (BUN), alanine aminotransferase (ALT) ALT and compared with CIS group. Besides, superoxide dismutase (SOD) and glutathione (GSH) levels were found increased as compared with CIS group. The ameliorating effects of CUR were presented with histopathological findings. Conclusions: CIS has serious toxicity on kidney and liver and oxidative stress play an important role on toxicity. The present study suggests that CUR has important healing effects on nephrotoxicity and hepatotoxicity of CIS.

PDF

___

1- Terada Y, Inoue K, Matsumoto T, Ishihara M, Hamada K, Shimamura Y. et al. 5- Aminolevulinic Acid Protects against Cisplatin-Induced Nephrotoxicity without Compromising the Anticancer Efficiency of Cisplatin in Rats In Vitro and In Vivo. PLoS One 2013, 6; 8: e80850.
2- Song J, Liu D1, Feng L, Zhang Z, Jia X, Xiao W. Protective Effect of Standardized Extract of Ginkgo biloba against Cisplatin-Induced Nephrotoxicity. Evid Based Complement Alternat Med 2013; 2013:846126.
3- Ajith TA, Usha S, Nivitha V. Ascorbic acid and alpha-tocopherol protect anticancer drug cisplatin induced nephrotoxicity in mice: a comparative study. Clin Chim Acta 2007; 375: 82-6.
4- Rubera I, Duranton C, Melis N, Cougnon M, Mograbi B, Tauc M. Role of CFTR in oxidative stress and suicidal death of renal cells during cisplatin-induced nephrotoxicity. Cell Death Dis 2013, 3; 4: e817.
5- Palipoch S, Punsawad C. Biochemical and histological study of rat liver and kidney injury induced by Cisplatin. J Toxicol Pathol 2013 ; 26: 293-9.
6- Ajith TA, Nivitha V, Usha S. Zingiber officinale Roscoe alone and in combination with alpha-tocopherol protect the kidney against cisplatin-induced acute renal failure. Food Chem Toxicol 2007; 45: 921-7.
7- Chirino YI, Pedraza-Chaverri J. Role of oxidative and nitrosative stress in cisplatininduced nephrotoxicity. Exp Toxicol Pathol 2009; 61: 223-42.
8- Yousef MI, Omar SA, El-Guendi MI, Abdelmegid LA. Potential protective effects of quercetin and curcumin on paracetamolinduced histological changes, oxidative stress, impaired liver and kidney functions and haematotoxicity in rat. Food Chem Toxicol 2010; 48: 3246-61.
9- Zhang H, Yu T, Wen L, Wang H, Fei D, Jin C. Curcumin enhances the effectiveness of cisplatin by suppressing CD133+ cancer stem cells in laryngeal carcinoma treatment. Exp Ther Med 2013; 6: 1317-21.
10- Mendonça LM, da Silva Machado C, Teixeira CC, de Freitas LA, Bianchi Mde L, Antunes LM. Curcumin reduces cisplatin-induced neurotoxicity in NGF-differentiated PC12 cells. Neurotoxicology 2013; 34: 205-11.
11- Gao S, Duan X, Wang X, Dong D, Liu D, Li X. et al. Curcumin attenuates arsenic-induced hepatic injuries and oxidative stress in experimental mice through activation of Nrf2 pathway, promotion of arsenic methylation and urinary excretion. Food Chem Toxicol 2013; 59: 739-47.
12- Trujillo J, Chirino YI, Molina-Jijón E, Andérica-Romero AC, Tapia E, PedrazaChaverrí J. Renoprotective effect of the antioxidant curcumin: Recent findings. Redox Biol 2013, 17; 1: 448-56.
13- Demougeot C, Marie C, Beley A: Importance of iron location in iron-induced hydroxyl radical production by brain slices. Life Sci 2000; 67: 399-41.
14- Sun Y, Oberley L, Li Y. A simple method for clinical assay of superoxide dismutase. Clin Chem 1988; 34:497-500.
15- Ellman GL: Tissue sulfhydryl groups. Arch Biochem Biophys 1959; 82: 70-77.
16- Ashrafi F, Nematbakhsh M, Safari T. A combination of vitamin C and losartan for cisplatin-induced nephrotoxicity in rats. Iran J Kidney Dis 2012; 6: 361-5.
17- Eren Z, Coban J, Ekinci ID. Evaluation of the effects of a high dose of erythropoietin-beta on early endotoxemia using a rat model. Adv Clin Exp Med 2012; 21: 321-9.
18- Beytur A, Köse E, Sarihan ME, Sapmaz HI, Dogan Z, Cetin A, et al. Beneficial effects of montelukast against cisplatin-induced acute renal damage in rats. Ren Fail 2012; 34: 343-9.
19- Kuhad A, Pilkhwal S, Sharma S, Tirkey N, Chopra K. Effect of curcumin on inflammation and oxidative stress in cisplatin-induced experimental nephrotoxicity. J Agric Food Chem 2007, 12; 55: 10150-5.
20- Ueki M, Ueno M, Morishita J, Maekawa N. Curcumin ameliorates cisplatin-induced nephrotoxicity by inhibiting renal inflammation in mice. J Biosci Bioeng 2013; 115: 547-51.
21- Antunes LM, Darin JD, Bianchi Nde L. Effects of the antioxidants curcumin or selenium on cisplatin-induced nephrotoxicity and lipid peroxidation in rats. Pharmacol Res 2001 ; 43: 145-50.
22- Nematbakhsh M, Pezeshki Z, Eshraghi-Jazi F, Ashrafi F, Nasri H, Talebi A, et al. Vitamin E, Vitamin C, or Losartan Is Not Nephroprotectant against Cisplatin-Induced Nephrotoxicity in Presence of Estrogen in Ovariectomized Rat Model. Int J Nephrol 2012; 2012: 284896.
23- Silici S, Ekmekcioglu O, Kanbur M, Deniz K. The protective effect of royal jelly against cisplatin-induced renal oxidative stress in rats. World J Urol 2011; 29: 127-32.
24- Waseem M, Kaushik P, Parvez S. Mitochondria-mediated mitigatory role of curcumin in cisplatin-induced nephrotoxicity. Cell Biochem Funct 2013; 31: 678-84.
25- Sener MT, Sener E, Tok A, Polat B, Cinar I, Polat H, et al. Biochemical and histologic study of lethal cisplatin nephrotoxicity prevention by mirtazapine. Pharmacol Rep 2012; 64: 594-602.
26- Maliakel DM, Kagiya TV, Nair CK. Prevention of cisplatin-induced nephrotoxicity by glucosides of ascorbic acid and alphatocopherol. Exp Toxicol Pathol 2008; 60: 521- 7.
27- Aldebasi YH, Aly SM, Rahmani AH. Therapeutic implications of curcumin in the prevention of diabetic retinopathy via modulation of anti-oxidant activity and genetic pathways. Int J Physiol Pathophysiol Pharmacol 2013, 15; 5: 194-202.
28- Gao S, Duan X, Wang X, Dong D, Liu D, Li X, et al. Curcumin attenuates arsenic-induced hepatic injuries and oxidative stress in experimental mice through activation of Nrf2 pathway, promotion of arsenic methylation and urinary excretion. Food Chem Toxicol 2013; 59: 739-47.
29- Hemeida RA, Mohafez OM. Curcumin attenuates methotraxate-induced hepatic oxidative damage in rats. J Egypt Natl Canc Inst 2008; 20: 141-8.
30- Ingawale DK, Mandlik SK, Naik SR. Models of hepatotoxicity and the underlying cellular, biochemical and immunological mechanism[s]: A critical discussion. Environ Toxicol Pharmacol 2013, 21; 37: 118-33.
31- Bentli R, Parlakpinar H, Polat A, Samdanci E, Sarihan ME, Sagir M. Molsidomine prevents cisplatin-induced hepatotoxicity. Arch Med Res 2013; 44: 521-8.
32- Lu Y, Cederbaum AI. Cisplatin-induced hepatotoxicity is enhanced by elevated expression of cytochrome P450 2E1. Toxicol Sci 2006; 89: 515-23.
33- Sun Y, Yang J, Wang LZ, Sun LR, Dong Q. Crocin attenuates cisplatin-induced liver injury in the mice. Hum Exp Toxicol 2014; 33: 855- 62.
34- Li G, Chen JB, Wang C, Xu Z, Nie H, Qin XY, et al. Curcumin protects against acetaminophen -induced apoptosis in hepatic injury. World J Gastroenterol 2013, 14; 19: 7440 -6.
35- Naik SR, Thakare VN, Patil SR. Protective effect of curcumin on experimentally induced inflammation, hepatotoxicity and cardiotoxicity in rats: evidence of its antioxidant property. Exp Toxicol Pathol 2011; 63: 419 -31.
36- Waseem M, Parvez S. Mitochondrial dysfunction mediated cisplatin induced toxicity: modulatory role of curcumin. Food Chem Toxicol 2013 ; 53: 334 -42.