Protective effect of crocin on gentamicin-induced nephrotoxicity in rats

Document Type : Original Article

Authors

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

2 Department of Pathology, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran

Abstract

Objective(s): Gentamicin is used for the treatment of Gram-negative bacterial infections. However, gentamicin administration is limited because of nephrotoxicity. The aim of the present study was to evaluate the protective effect of crocin against gentamicin-induced nephrotoxicity in rats.
Materials and Methods: Thirty two male Wistar rats received gentamicin (100 mg/kg, IP), with or without crocin (100 mg/kg, IP) for seven consecutive days. Plasma creatinine and urea-nitrogen concentrations, oxidative stress and histopathological changes of kidney tissues were monitored.
Results: Administration of gentamicin resulted in significant increases in plasma creatinine and urea-nitrogen concentrations and renal tissue malondialdehyde (MDA) level, and a decrease in the renal tissue ferric reducing/antioxidant power (FRAP) level. Crocin decreased plasma creatinine and urea-nitrogen concentrations and tissue MDA level, but increased the level of tissue FRAP. In addition, gentamicin led to cellular damages including glomerular atrophy, cellular desquamation, tubular necrosis and fibrosis, epithelial oedema of proximal tubules, perivascular edema, vascular congestion and intra-tubular proteinaceous casts, all of which were partially recovered by crocin.
Conclusion: Crocin has protective effects against functional disturbances, oxidative stress and tissue damages induced by gentamicin.

Keywords


1.Ali BH, Al Zaabi M, Blunden G, Nemmar Al. Experimental Gentamicin Nephrotoxicity and Agents that Modify it: A Mini-Review of Recent Research. Basic Clin Pharmacol Toxicol 2011; 109: 225-232.
2.Martinez-Salgado C, López-Hernández FJ, Lopez-Novoa JM. Glomerular nephrotoxicity of aminoglycosides. Toxicol Appl Pharmacol 2007; 223: 86-98.
3.Ali BH. Agents ameliorating or augmenting experimental gentamicin nephrotoxicity: some recent research. Food Chem Toxicol 2003; 41: 1447-1452.
4.Balakumar P, Rohilla A, Thangathirupathi A. Gentamicin-induced nephrotoxicity: do we have a promising therapeutic approach to blunt it? Pharmacol Res 2010; 62: 179-186.
5.Lopez-Novoa JM, Quiros Y, Vicente L, Morales AI, Lopez-Hernandez FJ. New insights into the mechanism of aminoglycoside nephrotoxicity: an integrative point of view. Kidney Int 2011; 79: 33-45.
6.Geleilete TJ, Melo GC, Costa RS, Volpini RA, Soares TJ, Coimbra TM. Role of myofibroblasts, macrophages, transforming growth factor-beta endothelin, angiotensin-II, and fibronectin in the progression of tubulointerstitial nephritis induced by gentamicin. J Nephrol 2001; 15: 633-642.
7.Tang WW, Feng L, Mathison JC, Wilson CB. Cytokine expression, upregulation of intercellular adhesion molecule-1, and leukocyte infiltration in experimental tubulointerstitial nephritis. Lab Invest 1994; 70: 631-638.
8.Wahl SM, Hunt DA, Wakefield LM, McCartney-Francis N, Wahl LM, Roberts AB, et al. Transforming growth factor type beta induces monocyte chemotaxis and growth factor production. Proc Natl Acad Sci USA 1987; 84: 5788-5792.
9.Anandan R, Subramanian P. Renal protective effect of hesperidin on gentamicin-induced acute nephrotoxicity in male Wistar albino rats. Redox Rep 2012; 17: 219-226.
10.Feyissa T, Asres K, Engidawork E. Renoprotective effects of the crude extract and solvent fractions of the leaves of Euclea divinorum Hierns against gentamicin-induced nephrotoxicity in rats. J Ethnopharmacol 2013; 145: 758-766.
11.Stojiljkovic N, Stoiljkovic M, Randjelovic P, Veljkovic S, Mihailovic D. Cytoprotective effect of vitamin C against gentamicin-induced acute kidney injury in rats. Exp Toxicol Pathol 2012; 64: 69-74.
12.Broushaki MT, Asadpour E, Sadeghnia HR, Dolati K. Effect of pomegranate seed oil against gentamicin-induced nephrotoxicity in rat. J Food Sci Technol 2012; 3510-3514.
13.Zheng YQ, Liu JX, Wang JN, Xu L. Effects of crocin on reperfusion-induced oxidative/nitrative injury to cerebral microvessels after global cerebral ischemia. Brain Res 2007; 1138: 86-94.
14.Hosseinzadeh H, Modaghegh MH, Safari Z. Crocus sativus L.(Saffron) extract and its active constituents (crocin and safranal) on ischemia-reperfusion in rat skeletal muscle. Evid Based Complement Alternat Med 2009; 6: 343-350.
15.Hosseinzadeh H, Sadeghnia HR, Ziaee T, Danaee A. Protective effect of aqueous saffron extract (Crocus sativus L.) and crocin, its active constituent, on renal ischemia-reperfusion-induced oxidative damage in rats. J Pharm Pharm Sci. 2005; 8: 387-393.
16.Naghizadeh B, Boroushaki MT, Vahdati Mashhadian N, Mansouri SMT. Protective effects of crocin against cisplatin-induced acute renal failure and oxidative stress in rats. Iran Biomed J 2008; 12: 93-100.
17.Nam KN, Park YM, Jung HJ, Lee JY, Min BD, Park SU, et al. Anti-inflammatory effects of crocin and crocetin in rat brain microglial cells. Eur J Pharmacol 2010; 648: 110-116.
18.Tamaddonfard E, Farshid AA, Eghdami K, Samadi F, Erfanparast A. Comparison of the effects of crocin, safranal and diclofenac on local inflammation and inflammatory pain responses induced by carrageenan in rats. Pharmacological Rep. 2013; 65: 1272-1280.
19.Lee IA, Lee JH, Baek NI, Kim DH. Antihyperlipidemic effect of crocin isolated from the fructus of Gardenia jasminoides and its metabolite crocetin. Biol Pharm Bull 2005; 28: 2106-2110.
20.Liakopoulou-Kyriakides M, Skubas AI. Characterization of the platelet aggregation inducer and inhibitor isolated from Crocus sativus. Biochem. Int. 1990; 22: 103-110.
21. Asdaq SMB, Inamdar MN. Potential of Crocus sativus (saffron) and its constituent, crocin, as hypolipidemic and antioxidant in rats. Appl biochem biotechnol 2010; 162: 358-372.
22.Najafi H, Firouzifar MR, Shafaat O, Changizi Ashtiyani S, Hosseini N. Protective effects of tribulus terrestris L extract against acute kidney injury induced by reperfusion injury in rats. Iran J Kidney Dis 2014; 8: 292-298.
23.Changizi Ashtiyani S, Najafi H, Jalalvandi S, Hosseinei F. Protective effects of Rosa canina L fruit extracts on renal disturbances induced by reperfusion injury in rats. Iran J kidney dis 2013; 7: 290-298.
24.Jafarey M, Changizi Ashtiyani S, Najafi H. Calcium dobesilate for prevention of gentamicin-induced nephrotoxicity in rats. Iran J Kidney Dis 2014; 8:                46-52.
25.Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979; 95: 351-358.
26.Benzie IF, Strain JJ. 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 1999; 299: 15-27.
27.Sternberg SS. Diagnostic Surgical Pathology. 3rd ed. Philadelphia: Lippincott: Williams & Wilkins; 1996 1701-1785.
28.Ysebaert DK, De Greef KE, Vercautern SR, Ghielli M, Verpooten GA, Eyskens EJ, et al. Identification and kinetics of leukocytes after severe ischaemia/reperfusion renal injury. Nephrol Dial Transplant 2000; 15: 1562-1574.
29.Balakumar P, Chakkarwar VA, Kumar V, Jain A, Reddy J, Singh M. Experimental models for nephropathy. J Renin Angiotensin Aldosterone Syst. 2008. 9: 189-195.
30.Maldonado PD, Barrera D, Rivero I, Mata R, Medina-Campos ON, Hernandez-Pando R, et al. Antioxidant sallylcysteine prevents gentamicin-induced oxidative stress and renal damage. Free Radic Biol Med 2003; 35: 317-324.
31.Walker PD, Barri Y, Shah SV. Oxidant mechanisms in gentamicin nephrotoxicity. Ren Fail 1999; 21: 433-442.
32.Zorov DB. Amelioration of aminoglycoside nephrotoxicity requires protection of renal mitochondria. Kidney Int 2010; 77: 841-843.
33.Pedraza-Chaverrı́ J, Maldonado PD, Medina Campos ON, Olivares-Corichi IM, Granados-Silvestre MA, Hernandez-Pando R, et al. Garlic ameliorates gentamicin nephrotoxicity: relation to antioxidant enzymes. Free Radic Biol Med 2000; 29: 602-611.
34.Hosseinzadeh H, Abootorabi A, Sadeghnia HR. Protective effect of crocus sativus stigma extract and crocin (trans-crocin 4) on Methyl Methanesulfonate–induced DNA damage in mice organs. DNA Cell Biol 2008; 27: 657-664.
35.Abdel-Raheem IT, Abdel-Ghany AA, Mohamed GA. Protective effect of quercetin against gentamicin-induced nephrotoxicity in rats. Biol Pharm Bull 2009; 32: 61-67.
36.Sardana A, Kalra S, Khanna D, Balakumar P. Nephroprotective effect of catechin on gentamicin-induced experimental nephrotoxicity. Clin Exp Nephrol 2014; 19:178-184.
37.Star RA. Treatment of acute renal failure. Kidney Int. 1998; 54: 1817-1831.
38.Xuan B, Zhou YH, Li N, Min ZD, Chiou GC. Effects of crocin analogs on ocular blood flow and retinal function. J Ocul Pharmacol Ther 1999; 15: 143-152.