Therapeutic effects of curcumin on the functional disturbances and oxidative stress induced by renal ischemia/reperfusion in rats

Document Type: Original Research Article

Authors

1 Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.

2 Department of Physiology, School of Medicine, Arak University of Medical Sciences, Arak, Iran.

3 Department of Nephrology, Emam Reza Hospital, Kermanshah University of Medical Sciences, Kermanshah, Iran.

4 School of pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Abstract

Objectives: Curcumin has anti-inflammatory and antioxidative properties. The objective of this study was to investigate the therapeutic effects of curcumin on functional disturbances, oxidative stress, and leukocyte infiltration induced by renal ischemia/reperfusion (I/R).
Materials and Methods: Animals were randomly divided into 9 groups. The groups with 24-h reperfusion consisted of sham-24h, I/R-24h, and three I/R groups treated with curcumin at 10, 20, or 30 mg kg-1, i.p. after the ischemic period. The 72-h reperfusion groups also included Sham-72h, I/R-72h, I/R treated with curcumin at single dose of 20 mg kg-1, i.p., and I/R group which received three doses of curcumin at 20 mg kg-1, i.p., consecutively. Renal functional injury was assessed by measuring serum creatinine and urea-nitrogen concentrations. Oxidative stress was evaluated by assessment tissue malondialdehyde (MDA) and the ferric reducing/antioxidant power (FRAP) levels. Moreover, renal tissue leukocyte infiltration was measured by histopathology examination.
Results: Ischemia/reperfusion resulted in a significant increase in serum concentration of creatinine, urea-nitrogen, tissue MDA level, and leukocytes infiltration as well as reduced FRAP level. Treatment with curcumin in 24-h reperfusion groups could only lead to a significant change in the levels of MDA and FRAP. However, in 72-h reperfusion groups, curcumin was able to correct all functional disturbances, oxidative stress, and leukocytes infiltration with more effectiveness in groups that received three doses of curcumin.
Conclusion: The administration of curcumin during 72-h reperfusion following 30 minutes of ischemia can decrease renal oxidative stress and leukocytes infiltration as well as improve kidney function. However, during first 24-h reperfusion, curcumin only decreased oxidative stress.

Keywords

Main Subjects

References

Ammon HP, Safayhi H, Mack T, Sabieraj J. 1993. Mechanism of antiinflammatory actions of curcumine and boswellic acids. J Ethnopharmacol, 38: 113-119.

Ammon HP, Wahl MA. 1991. Pharmacology of Curcuma longa. Planta Med, 57: 1-7.

Ashtiyani SC, Najafi H, Firouzifar MR, Shafaat O. 2013. Grape seed extract for reduction of renal disturbances following reperfusion in rats. Iran J Kidney Dis, 7: 28-35.

Ashtiyani SC, Najafi H, Kabirinia K, Vahedi E, Jamebozorky L. 2012. Oral omega-3 fatty acid for reduction of kidney dysfunction induced by reperfusion injury in rats. Iran J Kidney Dis, 6: 275-283.

Awad AS, El-Sharif AA. 2011. Curcumin immune-mediated and anti-apoptotic mechanisms protect against renal ischemia/reperfusion and distant organ induced injuries. Int Immunopharmacol, 11: 992-996.

Baek SM, Makabali GG, Brown RS, Shoemaker WC. 1975. Free-water clearance patterns as predictors and therapeutic guides in acute renal failure. Surgery, 77: 632-640.

Balogun E, Hoque M, Gong P, Killeen E, Green CJ, Foresti R, Alam J, Motterlini R. 2003. Curcumin activates the haem oxygenase-1 gene via regulation of Nrf2 and the antioxidant-responsive element. Biochem Journal, 371: 887-895.

Bayrak O, Uz E, Bayrak R, Turgut F, Atmaca AF, Sahin S, Yildirim ME, Kaya A, Cimentepe E, Akcay A. 2008. Curcumin protects against ischemia/reperfusion injury in rat kidneys. World J Urol, 26: 285-291.

Benzie IF, Strain JJ. 1999. Ferric reducing/antioxidant power assay: direct measure of total antioxidant activity of biological fluids and modified version for simultaneous measurement of total antioxidant power and ascorbic acid concentration. Methods Enzymol, 299: 15-27.

Changizi Ashtiyani S, Najafi H, Jalalvandi S, Hosseinei F. 2013. Protective effects of Rosa canina L fruit extracts on renal disturbances induced by reperfusion injury in rats. Iran J Kidney Dis, 7: 290-298.

Chatterjee PK, Patel NS, Sivarajah A, Kvale EO, Dugo L, Cuzzocrea S, et al. 2003. GW274150, a potent and highly selective inhibitor of iNOS, reduces experimental renal ischemia/reperfusion injury. Kidney Int, 63: 853-865.

Clarkson M, Friedewald J, Eustace J, Rabb H. 2008. Acute kidney injury. In: Brenner & Rector’s The Kidney. 8th ed. Philadelphia, Pennsylvania, USA: Saunders, Elsevier: 943-986.

Deodhar SD, Sethi R, Srimal RC. 1980. Preliminary study on antirheumatic activity of curcumin (diferuloyl methane). Indian J Med Res, 71: 632-634.

Granger DN. 1988. Role of xanthine oxidase and granulocytes in ischemia-reperfusion injury. Am J Physiol, 255: H1269-1275.

Hatcher H, Planalp R, Cho J, Torti FM, Torti SV. 2008. Curcumin: from ancient medicine to current clinical trials. Cell Mol Life Sci, 65: 1631-1652.

Jafarey M, Changizi Ashtiyani S, Najafi H. 2014. Calcium dobesilate for prevention of gentamicin-induced nephrotoxicity in rats. Iran J Kidney Dis, 8: 46-52.

Jayaprakasha GK, Jagan Mohan Rao L, Sakariah KK. 2002. Improved HPLC method for the determination of curcumin, demethoxycurcumin, and bisdemethoxycurcumin. J Agric Food Chem, 50: 3668-3672.

Kanai M. 2014. Therapeutic applications of curcumin for patients with pancreatic cancer. World J Gastroenterol, 20: 9384-9391.

Kim YS, Kwon JS, Cho YK, Jeong MH, Cho JG, Park JC, Kang JC, AHN Y. 2012. Curcumin reduces the cardiac ischemia-reperfusion injury: involvement of the toll-like receptor 2 in cardiomyocytes. J Nutr Biochem, 23: 1514-1523.

Kribben A, Edelstein CL, Schrier RW. 1999. Pathophysiology of acute renal failure. J Nephrol, 12 (Suppl 2): S142-151.

Kuhad A, Pilkhwal S, Sharma S, Tirkey N, Chopra K. 2007. Effect of curcumin on inflammation and oxidative stress in cisplatin-induced experimental nephrotoxicity. J Agric Food Chem, 55: 10150-10155.

Lal B, Kapoor AK, Agrawal PK, Asthana OP, Srimal RC. 2000. Role of curcumin in idiopathic inflammatory orbital pseudotumours. Phytother Res, 14: 443-447.

Lao CD, Ruffin MTt, Normolle D, Heath DD, Murray SI, Bailey JM, et al. 2006. Dose escalation of a curcuminoid formulation. BMC Complement Altern Med, 6: 10.

Masuda T, Hidaka K, Shinohara A, Maekawa T, Takeda Y, Yamaguchi H. 1999. Chemical studies on antioxidant mechanism of curcuminoid: analysis of radical reaction products from curcumin. J Agric Food Chem, 47: 71-77.

Moosavi SM, Ashtiyani SC, Hosseinkhani S. 2011. L-carnitine improves oxidative stress and suppressed energy metabolism but not renal dysfunction following release of acute unilateral ureteral obstruction in rat. Neurourol Urodyn, 30: 480-487.

Moosavi SM, Ashtiyani SC, Hosseinkhani S, Shirazi M. 2010. Comparison of the effects of L-carnitine and alpha-tocopherol on acute ureteral obstruction-induced renal oxidative imbalance and altered energy metabolism in rats. Urol Res, 38: 187-194.

Najafi H, Firouzifar MR, Shafaat O, Changizi Ashtiyani S, Hosseini N. 2014. Protective effects of Tribulus terrestris L extract against acute kidney injury induced by reperfusion injury in rats. Iran J Kidney Dis, 8: 292-298.

Ohkawa H, Ohishi N, Yagi K. 1979. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem, 95: 351-358.

Okudan N, Belviranli M, Gokbel H, Oz M, Kumak A. 2013. Protective effects of curcumin supplementation on intestinal ischemia reperfusion injury. Phytomedicine, 20: 844-848.

Prodjosudjadi W, Gerritsma JS, Klar-Mohamad N, Gerritsen AF, Bruijn JA, Daha MR, Van Es La. 1995. Production and cytokine-mediated regulation of monocyte chemoattractant protein-1 by human proximal tubular epithelial cells. Kidney Int, 48: 1477-1486.

Rogers NM, Stephenson MD, Kitching AR, Horowitz JD, Coates PT. 2012. Amelioration of renal ischaemia-reperfusion injury by liposomal delivery of curcumin to renal tubular epithelial and antigen-presenting cells. Br J Pharmacol, 166: 194-209.

Satoskar RR, Shah SJ, Shenoy SG. 1986. Evaluation of anti-inflammatory property of curcumin (diferuloyl methane) in patients with postoperative inflammation. Int J Clin Pharmacol Ther Toxicol, 24: 651-654.

Slofstra SH, Bijlsma MF, Groot AP, Reitsma PH, Lindhout T, Ten Cate H, et al. 2007. Protease-activated receptor-4 inhibition protects from multiorgan failure in a murine model of systemic inflammation. Blood, 110: 3176-3182.

Srimal RC, Dhawan BN. 1973. Pharmacology of diferuloyl methane (curcumin), a non-steroidal anti-inflammatory agent. J Pharm Pharmacol, 25: 447-452.

Thadhani R, Pascual M, Bonventre JV. 1996. Acute renal failure. N Engl J Med, 334: 1448-1460.

Tirkey N, Kaur G, Vij G, Chopra K. 2005. Curcumin, a diferuloylmethane, attenuates cyclosporine-induced renal dysfunction and oxidative stress in rat kidneys. BMC pharmacol, 50: 15.

Trujillo J, Chirino YI, Molina-Jijon E, Anderica-Romero AC, Tapia E, Pedraza-Chaverri J. 2013. Renoprotective effect of the antioxidant curcumin: Recent findings. Redox Biol, 1: 448-456.

Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J. 2007. Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol, 39: 44-84.

Winther K, Rein E, Kharazmi A. 1999. The anti-inflammatory properties of rose-hip. Inflammopharmacology, 7: 63-68.

Xu YX, Pindolia KR, Janakiraman N, Noth CJ, Chapman RA, Gautam SC. 1997. Curcumin, a compound with anti-inflammatory and anti-oxidant properties, down-regulates chemokine expression in bone marrow stromal cells. Exp Hematol, 25: 413-422.

Youn GS, Kwon DJ, Ju SM, Choi SY, Park J. 2013. Curcumin ameliorates TNF-alpha-induced ICAM-1 expression and subsequent THP-1 adhesiveness via the induction of heme oxygenase-1 in the HaCaT cells. BMB Rep, 46: 410-415.

Ysebaert DK, De Greef KE, Vercauteren SR, Ghielli M, Verpooten GA, Eyskens EJ, DE Broe ME. 2000. Identification and kinetics of leukocytes after severe ischaemia/reperfusion renal injury. Nephrol Dial Transplant, 15: 1562-1574.

Avicenna Journal of Phytomedicine

Volume 5, Issue 6
October 2015
Pages 576-586

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