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Ginger Extract Protect Iodinated Contrast Media Nephrotoxicity in rats through Modulation of Oxidative Stress, Cystain C, NGAL and TNF α


Affiliations
1 Chemistry Department, Zagazig University, Egypt
2 Biochemistry Division, Chemistry Department, Zagazig University, Egypt
     

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Background: Nephrotoxicity was reported in the initial clinical trials of contrast media. Aim of study: Our study was designed to evaluate the protective effect of ginger extract against nephrotoxicity induced by contrast agent. Material and Methods: Animals were divided into 5 groups as follow: Group1 (Control): They were not received any treatment during experiment period. Group2 (Ginger): Animals were deprived from water for 72 hours , then orally administrated with 400 mg/Kg/day of ginger extract for 72 hours. Group3 (protective): Animals were pre administrated orally with ginger extract with 400 mg/Kg for one week, then rats were deprived of water for 72 hours, then urografin was induced by a single (I.V.) at dose of 10mL per kg after that animals were orally administrated with 400 mg/Kg/day of ginger extract for 3 consecutive days. Group 4 (positive)(contrast media): Animals were induced by a single intravenous (I.V.) of urografin at dose of 10mL per kg after deprivation of water for 72 hours. Group 5(therapeutic): Animals rats were deprived of water for 72 hours, then Contrast-induced nephrotoxicity was induced (as group 4) , after that animals were post administrated with ginger extract 400 mg/Kg (for 3 days). Results: Administration contrast media caused significant elevation in serum urea, creatinine concentration, kidney tissue levels of MDA and NO. Also it caused significant increase in Cystain C , NGAL and TNFα levels. Also it significantly decreased SOD activity and GSH level. Treatment with Ginger extract restored the elevation of concentration of urea and creatinine, also oxidative stress markers in groups 3 and 5 and decreased Cystain C, NGAL and TNFα levels. Histopathological analysis confirmed that. Conclusion: ginger extract have a protective role in contrast media induced nephrotoxicity.

Keywords

Nephrotoicity, Diatrizoate, Ginger, Cystain C, NGAL, TNFα.
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  • Dugbartey G J and Redington A N . Prevention of contrastinduced nephropathy by limb ischemic preconditioning: underlying mechanisms and clinical effects American J Renal Physiology.2018; Mar 1;314(3): F319-F328.
  • wong Y P, LI Z, Guo J, Zhang A. Pathophysiology of contrastinduced nephropathy. Int J Cardiol .2012; 158:186-92.
  • Maliborski A, zukowski P, Nowicki G, Boguslawska R. Contrastinduced nephropathy a review of current literature and guidelines. Med Sci Monit. 2011; 17:199-204.
  • Yang JS, Peng YR, Tsai SC, Tyan YS, Lu CC, Chiu HY, Chiu YJ, Kuo SC, Tsai YF, Lin PC, Tsai FJ The molecular mechanism of contrast-induced nephropathy (CIN) and its link to in vitro studies on iodinated contrast media (CM). Biomedicine (Taipei). 2018; (1):1.
  • Heyman SN, Rosen S, Khamaisi M, Idee JM, Rosenberger C. Reactive oxygen species and the pathogenesis of radiocontrastinduced nephropathy. Invest Radiol .2010;45:188–195.
  • Akyol S, Ugurcu V, Altuntas A, et al .Caffeic acid phenethyl ester as a protective agent against nephrotoxicity and/or oxidative kidney damage: a detailed systematic review. ScientificWorldJournal; 2014, 561971.
  • Demin, G. and Yingying, Z. Comparative antibacterial activities of crude polysaccharides and flavonoids from Zingiber officinale and their extraction. American Journal of Tropical Medicine. 2010;5: 235-238.
  • Yiming, L., Van, H. T., Colin, C. D., and Basil, D. R. Preventive and Protective Properties of Zingiber officinale (Ginger) in Diabetes Mellitus, Diabetic Complications, and Associated Lipid and Other Metabolic Disorders: A Brief Review. Evidence-Based Complementary and Alternative Medicine, 2012(516870): 1–10.
  • Surh, Y.J. Food Chem Toxicol. 2002; 40, 1091-1097.
  • Morakinyo A. O, Akindele A J, Ahmed Z . Modulation of Antioxidant Enzymes and Inflammatory Cytokines: Possible Mechanism of Anti-diabetic Effect of Ginger Extracts. Afr. J. Biomed.2011; 195 -202.
  • Tabacco.A., meiattinif., moda E., and Tarlip . simplified enzymatic colormetric serum urea nitrogen determination . clin. Chem. 1979; 25:336-337.
  • Hennery R.J. Cannon D.C. and winkelm J.W. clinical chemistry : principles and technique , 2nd ed., new york, harper and Row ; pp.1974; 422-424.
  • Montgomery, H.A.C. and dymock, J.F. The determination of nitrite in water . Analyst 1961; 86:41.416.
  • Ohkawa, H., oishi N. and Yagi , K. Anal . Biochem.,1979; 95:351.
  • Beutler, E., duron ,O. and Kelly ,M.B. Improved method for the determination of blood glutathione .J.lab. clin.Med.,1963; 61: 882-890.
  • Nishikimi, M., Rao, N. A. and Yagi, K. The occurrence of superoxide anion in the reaction of reduced phenazine methosulfate and molecular oxygen. Biochem. Biophys. Res. Commun.1972; 46, 849-854.
  • Levesque, R. Programming and Data Management for SPSS Statistics 17.0: A Guide for SPSS Statistics and SAS Users. SPSS, Chicago 2007.
  • YeniceriogluY,Yilmaz O, Sarioglu S et al. Effects of Nacetylcysteine on radio contrast nephropathy in rats. Scand J Urol Nephrol. 2006; 40: 63–69.
  • Wang YX, Jia YF, Chen KM et al. Radiographic contrast media induced nephropathy: experimental observations and the protective effect of calcium channel blockers. Br J Radiol. 2001; 74: 1103–1108.
  • Deray G, Baumelou B, Martinez F et al . Renal vasoconstriction after low and high osmolar contrast agents in ischemic and nonischemic canine kidney. Clin Nephrol .1991; 36: 93–96.
  • Toprak O, Cirit M. Risk factors for contrast-induced nephropathy. Kidney Blood Press Res. 2006; 29: 84–93.
  • Salih Inal S, Koc E, Okyay G U, Özge T. Pasaoglu, Gönül I I, Oyar E O, Pasaoglu H, Güz G. Protective effect of adrenomedullin on contrast induced nephropathy in rats. Nefrologia. 2014;34(6):724-31.
  • Toprak O, Cirit M, Tanrisev M, Yazici C, Canoz O, Sipahioglu M, Uzum A , Ersoy R and Sozmen E Y. Preventive effect of nebivolol on contrast-induced nephropathy in rats. Nephrol Dial Transplant 2008; 23: 853–859.
  • Azu, O.O.; Francis, I.O.D.; Abraham, A.O.; Crescie, C.N.; Stephen, O.E. and Abayomi, O.O. Protective Agent, Kigelia Africana Fruit Extract, Against Cisplatin-Induced Kidney Oxidant Injury in Sprague–Dawley Rats. Asian J Pharma Clin Res.2010; 3: 84-88.
  • Anusuya, N.; P. Durgadevi,; A. Dhinek and S. Mythily. Nephroprotective effect of ethanolic extract of garlic (Allium sativum L.) on cisplatin induced nephrotoxicity in male wistar rats. Asian J Pharm Clin Res.2013; Vol 6 : 97-100
  • Dickey, D.T.; Muldoon, L.L.; Doolittle, N.D.; Peterson, D.R. ; Kraemer D.F. and Neuwelt, E.A. Effect of N-acetylcysteine route of administration on chemoprotection against cisplatininducedtoxicity in rat models. Cancer Chemotherapy Pharmacol., 2008; 62: 235-241.
  • Azmus AD, Gottschall C, Manica A, Manica J, Duro K, Frey M, Bulcao L, Lima C. Effectiveness of acetylcysteine in prevention of contrast nephropathy. The Journal of invasive cardiology . 2005;17:80-84.
  • Baker CS, Wragg A, Kumar S, De Palma R, Baker LR, Knight CJ. A rapid protocol for the prevention of contrast-induced renal dysfunction: The rappid study. Journal of the American College of Cardiology. 2003;41:2114-2118.
  • Hou J, Yan G, Liu B, Zhu B, Qiao Y, Wang D, Li R, Luo E, Tang C. The Protective Effects of Enalapril Maleate and Folic Acid Tablets against Contrast-Induced Nephropathy in Diabetic Rats. Biomed Res Int. ; Feb 7;2018:4609750.
  • GongX, Duan Y, Zheng J, Wang Y, Wang G, Norgren S, and Tom K. Hei. Nephroprotective Effects of N-Acetylcysteine Amide against Contrast-Induced Nephropathy through Upregulating Thioredoxin-1, Inhibiting ASK1/p38MAPK Pathway, and Suppressing Oxidative Stress and Apoptosis in Rats. 2016; 8715185.
  • Yue R, Zuo C, Zeng J, Su B, Tao Y, Huang S, Zeng R. Atorvastatin attenuates experimental contrast-induced acute kidney injury: a role for TLR4/MyD88 signaling pathway. Ren Fail. 2017; Nov;39(1):643-651.
  • Nasri H, Nematbakhsh M, Ghobadi S, Ansari R, Najmeh S Shahinfard and -kopaei M R . Preventive and Curative Effects of Ginger Extract Against Histopathologic Changes of GentamicinInduced Tubular Toxicity in Rats. International journal of preventive medicine. 2013; 4(3):316-21.
  • Krim M, Messaadia A, Maidi I, Aouacheri O, Saka S . Protective effect of ginger against toxicity induced by chromate in rats. Ann Biol Clin.2013; 71 (2): 165-73.
  • Shimizu MH, Araujo M, Borges SM, de Tolosa EM, Seguro AC. Influence of age and vitamin E on post-ischemic acute renal failure. Exp Gerontol. 2004;39(5):825-30.
  • Tepel M, van der Giet M, Schwarzfeld C, Laufer U, Liermann D, Zidek W. Prevention of radiographic-contrast-agent-induced reductions in renal function by acetylcysteine. N Engl J Med . 2000; 343(3):180-4.
  • Aspelin P, Aubry P, Fransson SG, Strasser R, Willenbrock R, Berg KJ. Nephrotoxic effects in high-risk patients undergoing angiography. N Engl J Med. 2003;348(6):491-9.
  • Asif A, Epstein M. Prevention of radiocontrast-induced nephropathy. Am J Kidney Dis .2004;44:12–24.
  • Detrenis S, Meschi M, Musini S,Savazzi G. Lights and shadows on the pathogenesis of contrast-induced nephropathy: State of the art. Nephrol Dial Transplant.2005;20:1542–1550.
  • Wang N, R.-B. Wei, Q.-P. Li et al. “Renal protective effect of probucol in rats with contrast-induced nephropathy and its underlying mechanism,” Medical Science Monitor, 2015;vol. 21, pp. 2886–2892.
  • Tasanarong A, Kongkham S, and Itharat A. “Antioxidant effect of Phyllanthus emblica extract prevents contrast-induced acute kidney injury,” BMC Complementary and Alternative Medicine,2014; vol. 14, article 138.
  • Thomas DD, Espey MG, Ridnour LA, et al. Hypoxic inducible factor 1alpha, extracellular signal-regulated kinase, and p53 are regulated by distinct threshold concentrations of nitric oxide. Proc Natl Acad Sci U S A. 2004;101:8894–8899.
  • Hannibal L. et al. Nitric oxide homeostasis in neurodegenerative diseases. Curr Alzheimer Res.2016;13:135–149.
  • Quintavalle C, Brenca M, De MiccoF, et al. In vivo and in vitro assessment of pathways involved in contrast media-induced renal cells apoptosis. Cell Death Dis.2011;2:155.
  • Aksu F, Aksu B, Unlu N, Karaca T, Ayvaz S, Erman H, Uzun H, Keles N, Bulur S and Unlu E (2016) . Antioxidant and renoprotective effects of sphingosylphosphorylcholine on contrast-induced nephropathy in rats . Renal Failure J. 2016; 38:110.
  • Karaman A, Diyarbakir B, Subasi I D, Kose D, BilginA O, Topcu A, Gundogdu C, Karakaya A D, Aktutan Z B and Alper F(2016). A novel approach to contrast-induced nephrotoxicity: the melatonergic agent agomelatine . Br J Radiol 2016; 89: 20150716.
  • Baykara M, Silici S, Özçelik M, Güler O, Erdoğan N, Bilgen M. In vivo nephroprotective efficacy of propolis against contrastinduced nephropathy . Diagn Interv Radiol. 2015; 21: 317–321.
  • Francisco A. P, Mara M. G. Prata M.G, Oliveira I.C M, Alves N T Q, R E M, Monteiro H S A , Silva J A, Vieira P C, Viana D A, A B , and Havt. Gingerol Fraction from Zingiber officinale Protects against Gentamicin-Induced Nephrotoxicity. Antimicrob Agents Chemother. 2014;Apr; 58(4): 1872–1878.
  • Ippoushi K, Azuma K, Ito H, Horie H, Higashio H. [6]-Gingerol inhibits nitric oxide synthesis in activated J774.1 mouse macrophages and prevents peroxynitrite-induced oxidation and nitration reactions. Life Sci. 2003;Nov 14;73(26):3427-37.
  • Ghasemzadeh A, Jaafar HZ, Rahmat A. Antioxidant activities, total phenolics and flavonoids content in two varieties of Malaysia young ginger (Zingiber officinale Roscoe). Molecules. 2010; Jun 14;15(6):4324-33.
  • Shanmugam KR, Ramakrishna CH, Mallikarjuna K, Reddy KS. Protective effect of ginger against alcohol-induced renal damage and antioxidant enzymes in male albino rats. Indian J Exp Biol. 2010; Feb;48(2):143-9.
  • Danwilai K , Konmun J., Sripanidkulchai B O, and Subongkot S. Antioxidant activity of ginger extract as a daily supplement in cancer patients receiving adjuvant chemotherapy: a pilot study. Cancer Manag Res. 2017; 9: 11–18.
  • Kato K, Sato N, Yamamoto T, Iwasaki YK, Tanaka K, Mizuno K. Valuable markers for contrast-induced nephropathy in patients undergoing cardiac catheterization. Circ J.2008 ;72:1499–1505.
  • Kaseda R, Iino N, Hosojima M, et al. Megalin-mediated endocytosis of cystatin C in proximal tubule cells. Biochem Biophys Res Commun. 2007;357(4):1130–1134.
  • Zhang J Z, Kang X J, Gao Y, Zheng Y Y, Wu T T, Li L, Liu F, Yang Y N, Xiao-Mei Li X M, Ma Y T and XieX. Efficacy of alprostadil for preventing of contrast-induced nephropathy: A meta-analysis. Scientific Reports; 2017: 1045.
  • Wang M, Zhang L, Yue R, You G, and Zeng R . Significance of Cystatin C for Early Diagnosis of Contrast-Induced Nephropathy in Patients Undergoing Coronary Angiography. Med Sci Monit..2016;22: 2956–2961.
  • Zhang Z, Lu B, Sheng X, Jin N. Cystatin C in prediction of acute kidney injury: a systemic review and meta-analysis. Am J Kidney Dis. 2011;58:356–365.
  • Briguori C, Visconti G, Rivera NV, Focaccio A, Golia B, Giannone R, Castaldo D, De Micco F, Ricciardelli B, Colombo A. Cystatin C and contrast-induced acute kidney injury. Circulation.2010;121:2117–2122.
  • Kuwabara T, Mori K, Mukoyama M, et al. Urinary neutrophil gelatin-ase-associated lipocalin levels reflect damage to glomeruli, proximal tubules, and distal nephrons. Kidney Int. 2009;75(3):285–294.
  • Hvidberg V, Jacobsen C, Strong RK, Cowland JB, Moestrup SK, Borregaard N.The endocytic receptor megalin binds the iron transporting neutrophil-gelatinase-associated lipocalin with high affinity and mediates its cellular uptake. FEBS Lett. 2005, 579(3):773–777.
  • Mishra J, Ma Q, Kelly C, Mitsnefes M, Mori K, Barasch J, Devarajan P . Kidney NGAL is a novel early marker of acute injury following transplantation. Pediatr Nephrol.2006; 21:856– 863.
  • Rosenthal S H, Marggraf G, Husing J, et al. Early detection of acute renal failure by serum cystatin C. Kidney Int.2004 ;66(3):1115–1122.
  • Xu S and Venge P . Lipocalins as biomarkers of disease. Biochim Biophys Acta .2000;1482:298–307 .
  • Charlton JR, Portilla D and Okusa MD. A basic science view of acute kidney injury biomarkers. Nephrol Dial Transplant.2014 ;29(7):1301–1311.
  • Kafkas N, Liakos C, Zoubouloglou F, Dagadaki O, Dragasis S, Makris K . Neutrophil Gelatinase-Associated Lipocalin as an Early Marker of Contrast-Induced Nephropathy After Elective Invasive Cardiac Procedures. Clin Cardiol. 2016;Aug;39(8):46470.
  • Cadirci E, Altunkaynak BZ, Halici Z, Odabasoglu F, Uyanik MH, Gundogdu C, et al. Alpha-lipoic acid as a potential target for the treatment of lung injury caused by cecal ligation and punctureinduced sepsis model in rats. Shock.2010; 33: 479–84.
  • Yayla M, Halici Z, Unal B, Bayir Y, Akpinar E and Gocer F. Protective effect of Et-1 receptor antagonist bosentan on paracetamol induced acute liver toxicity in rats. Eur J Pharmacol. 2014; 726: 87–95.
  • Zhou ZX, Wang LP, Song ZY, Lambert JC, McClain CJ, Kang YJ. A critical involvement of oxidative stress in acute alcoholinduced hepatic TNF-alpha production. Am J Pathol.2003; 163: 1137–46.
  • Kuhad A and Chopra K. Attenuation of diabetic nephropathy by tocotrienol: Involvement of NFkB signaling pathway. Life Sci.2009; 84: 296–301.
  • Gazi S, Altun A, Erdogan O. Contrast induced nephropathy: preventive and protective effects of melatonin. J Pineal Res.2006; 41: 53–7.
  • Palabiyik S S., Dincer B, Cadirci E, Cinar I, Gundogdu C, Polat B, Yayla M andHalici Z . A new update for radiocontrast-induced nephropathy aggravated with glycerol in rats: the protective potential of epigallocatechin-3-gallate . renal failure j. 2017;39:314-322
  • Kunakv C S, Ugan R A , Cadirci E , Karakus E, Polat B, Un H , Halici Z, Sritemur M, Atmacah T and Karaman A. Nephroprotective potential of carnitine against glycerol and contrast-induced kidney injury in rats through modulation of oxidative stress, proinflammatory cytokines, and apoptosis . BJR . 2016;89 (1058):20140724.
  • Shirpoor A, Hasan M, Ilkhanizadeh B, Ansari KH, Nemati S . Protective Effects of Ginger (Zingiber officinale) Extract against Diabetes-Induced Heart Abnormality in Rats. Diabetes Metab J. 2016 Feb; 40(1): 46–53.
  • Ebru Uz , Omer Faruk Karatas , Emin Mete and Ali Akcay . The Effect of Dietary Ginger ( Zingiber officinals Rosc) on Renal Ischemia/Reperfusion Injury in Rat Kidneys.2009;31: 251-260
  • Zhao B, Zhao O, Li J, Xing T, Wang F, Wang N. Renalase Protects against Contrast-Induced Nephropathy in SpragueDawley Rats. PLOS ONE J.2015; Jan 30 .
  • Ari E, A E Kedrah, MD, Y Alahdab, MD, G Bulut, MD, Z Eren, MD, O Baytekin, MD, and D Odabasi, MD . Antioxidant and renoprotective effects of paricalcitol on experimental contrastinduced nephropathy model. Br J Radiol. 2012;Aug; 85(1016): 1038–1043.
  • Gabr S A, Alghadir A H . Biological activities of ginger against cadmium-induced renal toxicity. Saudi Journal of Biological Sciences.2017 .
  • Lakshmi B.V.S and Sudhakar M, (2010). Protective Effect of Zingiber officinale on Gentamicin-Induced Nephrotoxicity in Rats.International Journal of Pharmacology,2010; 6: 58-62.

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  • Ginger Extract Protect Iodinated Contrast Media Nephrotoxicity in rats through Modulation of Oxidative Stress, Cystain C, NGAL and TNF α

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Authors

Mohamed H. Sherif
Chemistry Department, Zagazig University, Egypt
Al-Shimaa M. Abas
Biochemistry Division, Chemistry Department, Zagazig University, Egypt
Lobna A. Zaitoun
Biochemistry Division, Chemistry Department, Zagazig University, Egypt

Abstract


Background: Nephrotoxicity was reported in the initial clinical trials of contrast media. Aim of study: Our study was designed to evaluate the protective effect of ginger extract against nephrotoxicity induced by contrast agent. Material and Methods: Animals were divided into 5 groups as follow: Group1 (Control): They were not received any treatment during experiment period. Group2 (Ginger): Animals were deprived from water for 72 hours , then orally administrated with 400 mg/Kg/day of ginger extract for 72 hours. Group3 (protective): Animals were pre administrated orally with ginger extract with 400 mg/Kg for one week, then rats were deprived of water for 72 hours, then urografin was induced by a single (I.V.) at dose of 10mL per kg after that animals were orally administrated with 400 mg/Kg/day of ginger extract for 3 consecutive days. Group 4 (positive)(contrast media): Animals were induced by a single intravenous (I.V.) of urografin at dose of 10mL per kg after deprivation of water for 72 hours. Group 5(therapeutic): Animals rats were deprived of water for 72 hours, then Contrast-induced nephrotoxicity was induced (as group 4) , after that animals were post administrated with ginger extract 400 mg/Kg (for 3 days). Results: Administration contrast media caused significant elevation in serum urea, creatinine concentration, kidney tissue levels of MDA and NO. Also it caused significant increase in Cystain C , NGAL and TNFα levels. Also it significantly decreased SOD activity and GSH level. Treatment with Ginger extract restored the elevation of concentration of urea and creatinine, also oxidative stress markers in groups 3 and 5 and decreased Cystain C, NGAL and TNFα levels. Histopathological analysis confirmed that. Conclusion: ginger extract have a protective role in contrast media induced nephrotoxicity.

Keywords


Nephrotoicity, Diatrizoate, Ginger, Cystain C, NGAL, TNFα.

References