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EGCG inhibit chemical reactivity of iron through forming an Ngal–EGCG–iron complex

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Abstract

Accumulated evidence indicates that the interconversion of iron between ferric (Fe3+) and ferrous (Fe2+) can be realized through interaction with reactive oxygen species in the Fenton and Haber–Weiss reactions and thereby physiologically effects redox cycling. The imbalance of iron and ROS may eventually cause tissue damage such as renal proximal tubule injury and necrosis. Many approaches were exploited to ameliorate the oxidative stress caused by the imbalance. (−)-Epigallocatechin-3-gallate, the most active and most abundant catechin in tea, was found to be involved in the protection of a spectrum of renal injuries caused by oxidative stress. Most of studies suggested that EGCG works as an antioxidant. In this paper, Multivariate analysis of the LC–MS data of tea extracts and binding assays showed that the tea polyphenol EGCG can form stable complex with iron through the protein Ngal, a biomarker of acute kidney injury. UV–Vis and Luminescence spectrum methods showed that Ngal can inhibit the chemical reactivity of iron and EGCG through forming an Ngal–EGCG–iron complex. In thinking of the interaction of iron and ROS, we proposed that EGCG may work as both antioxidant and Ngal binding siderphore in protection of kidney from injuries.

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References

  • Abdel-Raheem IT, El-Sherbiny GA, Taye A (2010) Green tea ameliorates renal oxidative damage induced by gentamicin in rats. Pak J Pharm Sci 23:21–28

    PubMed  CAS  Google Scholar 

  • Balentine DA, Wiseman SA, Bouwens LC (1997) The chemistry of tea flavonoids. Crit Rev Food Sci 37:693–704

    Article  CAS  Google Scholar 

  • Bao G, Clifton M, Hoette TM, Mori K et al (2010) Iron traffics in circulation bound to a siderocalin (Ngal)–catechol complex. Nat Chem Biol 6:602–609

    Article  PubMed  CAS  Google Scholar 

  • de Vries B, Walter SJ, von Bonsdorff L, Wolfs TGAM et al (2004) Reduction of circulating redox-active iron by apotransferrin protects against renal ischemia–reperfusion injury. Transplantation 77:669–675

    Article  PubMed  Google Scholar 

  • El-Mowafy AM, Al-Gayyar MM, Salem HA, El-Mesery ME, Darweish MM (2010) Novel chemotherapeutic and renal protective effects for the green tea (EGCG): role of oxidative stress and inflammatory-cytokine signaling. Phytomedicine 17:1067–1075

    Article  PubMed  CAS  Google Scholar 

  • Fujitsuka N, Yokozawa T, Oura H, Nakamura K, Ienaga K (1994) Major role of hydroxyl radical in the conversion of creatinine to creatol. Nephron 68:280–281

    Article  PubMed  CAS  Google Scholar 

  • Gao J, Zhao H, Hylands PJ, Corcoran O (2010) Secondary metabolite mapping identifies scutellaria inhibitors of human lung cancer cells. J Pharmaceut Biomed 53:723–728

    Article  CAS  Google Scholar 

  • Hisamura F, Kojima-Yuasa A, Kennedy DO, Matsui-Yuasa I (2006) Protective effect of green tea extract and tea polyphenols against FK506-induced cytotoxicity in renal cells. Basic Clin Pharmacol 98:192–196

    Article  CAS  Google Scholar 

  • Hoette TM, Abergel RJ, Xu J, Strong RK, Raymond KN (2008) The role of electrostatics in siderophore recognition by the immunoprotein siderocalin. J Am Chem Soc 130:17584–17592

    Article  PubMed  CAS  Google Scholar 

  • Holmes MA, Paulsene W, Jide X, Ratledge C, Strong RK (2005) Siderocalin (Lcn 2) also binds carboxymycobactins, potentially defending against mycobacterial infections through iron sequestration. Structure 13:29–41

    Article  PubMed  CAS  Google Scholar 

  • Horwitz LD, Sherman NA, Kong Y, Pike AW et al (1998) Lipophilic siderophores of mycobacterium tuberculosis prevent cardiac reperfusion injury. Proc Natl Acad Sci USA 95:5263–5268

    Article  PubMed  CAS  Google Scholar 

  • Iwahashi H, Morishita H, Ishii T, Sugata R, Kido R (1989) Enhancement by catechols of hydroxyl-radical formation in the presence of ferric ions and hydrogen peroxide. J Biochem 105:429–434

    PubMed  CAS  Google Scholar 

  • Jang YH, Lee YC, Park NH, Shin HY et al (2006) Polyphenol (−)-epigallocatechin gallate protection from ischemia/reperfusion-induced renal injury in normotensive and hypertensive rats. Transpl P 38:2190–2194

    Article  CAS  Google Scholar 

  • Kehrer JP (2000) The Haber–Weiss reaction and mechanisms of toxicity. Toxicology 149:43–50

    Article  PubMed  CAS  Google Scholar 

  • Ling TJ, Wan XC, Ling WW, Zhang ZZ et al (2010) New triterpenoids and other constituents from a special microbial-fermented tea-Fuzhuan brick tea. J Agric Food Chem 58:4945–4950

    Article  PubMed  CAS  Google Scholar 

  • Mishra J, Dent C, Tarabishi R, Mitsnefes MM et al (2005) Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury after cardiac surgery. Lancet 365:1231–1238

    Article  PubMed  CAS  Google Scholar 

  • Mori K, Lee HT, Rapoport D, Drexler IR et al (2005) Endocytic delivery of lipocalin–siderophore–iron complex rescues the kidney from ischemia–reperfusion injury. J Clin Invest 115:610–621

    PubMed  CAS  Google Scholar 

  • Nguyen HN, Dejaegher B, Tistaert C, Nguyen THV et al (2009) Development of HPLC fingerprints for Mallotus species extracts and evaluation of the peaks responsible for their antioxidant activity. J Pharmaceut Biomed 50:753–763

    Article  Google Scholar 

  • Nickolas TL, O’Rourke MJ, Yang J, Sise ME et al (2008) Sensitivity and specificity of a single emergency department measurement of urinary neutrophil gelatinase-associated lipocalin for diagnosing acute kidney injury. Ann Intern Med 148:810–819

    Article  PubMed  Google Scholar 

  • Paller MS, Hedlund BE (1994) Extracellular iron chelators protect kidney cells from hypoxia/reoxygenation. Free Radic Biol Med 17:597–603

    Article  PubMed  CAS  Google Scholar 

  • Paller MS, Hoidal JR, Ferris TF (1984) Oxygen free radicals in ischemic acute renal failure in the rat. J Clin Invest 74:1156–1164

    Article  PubMed  CAS  Google Scholar 

  • Peng A, Ye T, Rakheja D, Tu Y et al (2011) The green tea polyphenol (−)-epigallocatechin-3-gallate ameliorates experimental immune-mediated glomerulonephritis. Kidney Int 80:601–611

    Article  PubMed  CAS  Google Scholar 

  • Rah DK, Han DW, Baek HS, Hyon SH et al (2007) Protection of rabbit kidney from ischemia/reperfusion injury by green tea polyphenol pretreatment. Arch Pharm Res 30:1447–1454

    Article  PubMed  CAS  Google Scholar 

  • Rehman H, Krishnasamy Y, Haque K, Thurman RG et al (2013) Green tea polyphenols stimulate mitochondrial biogenesis and improve renal function after chronic cyclosporin a treatment in rats. PLoS One 8:e65029. doi:10.1371/journal.pone.0065029

    Article  PubMed  CAS  Google Scholar 

  • Rodríguez J, Parra C, Contreras FJ, Baeza J (2001) Dihydroxybenzenes: driven Fenton reactions. Water Sci Technol 44:251–256

    PubMed  Google Scholar 

  • Roudkenar MH, Kuwahara Y, Baba T, Roushandeh AM, Ebishima S, Abe S, Ohkubo Y, Fukumoto M (2007) Oxidative stress induced lipocalin 2 gene expression: addressing its expression under the harmful conditions. J Radiat Res 48:39–44

    Article  PubMed  CAS  Google Scholar 

  • Ruiz S, Pergola PE, Zager RA, Vaziri ND (2013) Targeting the transcription factor Nrf2 to ameliorate oxidative stress and inflammation in chronic kidney disease. Kidney Int 83:1029–1041

    Article  PubMed  CAS  Google Scholar 

  • Ryu HH, Kim HL, Chung JH, Lee BR et al (2011) Renoprotective effects of green tea extract on renin–angiotensinaldosterone system in chronic cyclosporine-treated rats. Nephrol Dial Transpl 26:1188–1193

    Article  CAS  Google Scholar 

  • Setsukinai K, Urano Y, Kakinuma K, Majima HJ, Nagano T (2003) Development of novel fluorescence probes that can reliably detect reactive oxygen species and distinguish specific species. J Biol Chem 278:170–3175

    Article  Google Scholar 

  • Shedlofsky SI (1998) Role of iron in the natural history and clinical course of hepatitis C disease. Hepatogastroenterol 20:349–355

    Google Scholar 

  • Shi S, Zheng S, Zhu Y, Jia C, Xie H (2003) Inhibitory effect of tea polyphenols on renal cell apoptosis in rat test subjects suffering from cyclosporine-induced chronic nephrotoxicity. Chin Med J (Engl) 116:1345–1350

    CAS  Google Scholar 

  • Shyur LF, Yang NS (2008) Metabolomics for phytomedicine research and drug development. Curr Opin Chem Biol 12:66–71

    Article  PubMed  CAS  Google Scholar 

  • Ulrich HE (2010) 3.23 Chemistry of tea, comprehensive natural products II chemistry and biology, volume 3: development and modification of bioactivity. Elsevier Ltd, Oxford, United Kingdom, pp 999–1032

  • Wills MR (1985) Uremic toxins, and their effect on intermediary metabolism. Clin Chem 31:5–13

    PubMed  CAS  Google Scholar 

  • Wu CC, Hsu MC, Hsieh CW, Lin JB et al (2006) Upregulation of heme oxygenase-1 by epigallocatechin-3-gallate via the phosphatidylinositol 3-kinase/Akt and ERK pathways. Life Sci 78:2889–2897

    Article  PubMed  CAS  Google Scholar 

  • Xia JG, Wishart DS (2011) Web-based inference of biological patterns, functions and pathways from metabolomic data using MetaboAnalyst. Nat Protoc 6:743–760

    Article  PubMed  CAS  Google Scholar 

  • Xia JG, Psychogios N, Young N, Wishart DS (2009) MetaboAnalyst: a web server for metabolomic data analysis and interpretation. Nucleic Acids Res 37:W652–W660

    Article  PubMed  CAS  Google Scholar 

  • Yokozawa T, Fujitsuka N, Oura H (1991) Studies on the precursor of methylguanidine in rats with renal failure. Nephron 58:90–94

    Article  PubMed  CAS  Google Scholar 

  • Yokozawa T, Cho EJ, Nakagawa T (2003) Influence of green tea polyphenol in rats with arginine-induced renal failure. J Agric Food Chem 51:2421–2425

    Article  PubMed  CAS  Google Scholar 

  • Zhang X, Lemasters JJ (2013) Translocation of iron from lysosomes to mitochondria during ischemia predisposes to injury after reperfusion in rat hepatocytes. Free Rad Biol Med 63:243–253

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

Financial assistance was received with appreciation from China National Science Foundation 81170654/H0507, Anhui Agricultural University Talents Foundation (YJ2011-06), Anhui Outstanding Youth Science Foundation 1108085J04, and Program for Changjiang Scholars and Innovative Research Team in University IRT1101.

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The authors have declared no conflict of interest.

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Correspondence to Guan-Hu Bao.

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Bao, GH., Xu, J., Hu, FL. et al. EGCG inhibit chemical reactivity of iron through forming an Ngal–EGCG–iron complex. Biometals 26, 1041–1050 (2013). https://doi.org/10.1007/s10534-013-9681-8

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  • DOI: https://doi.org/10.1007/s10534-013-9681-8

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