title: Targeting HO-1 by Epigallocatechin-3-Gallate Reduces Contrast-Induced Renal Injury via Anti-Oxidative Stress and Anti-Inflammation Pathways.
abstract: Both oxidative stress and inflammation are involved in the pathogenesis of contrast-induced nephropathy (CIN). Epigallocatechin-3-gallate (EGCG), a purified catechin from green tea, has antioxidant and anti-inflammatory effects. However, it is unknown whether or not EGCG is effective in treating CIN. Our present study found that intravenous administration of EGCG, either before or just after the establishment of CIN, had a protective effect, determined by normalization of serum creatinine and blood urea nitrogen levels, improvement in renal histopathological scoring and alleviation of apoptosis, accompanied by decreased oxidative stress and inflammation. Because EGCG is a potent inducer of the antioxidant heme oxygenase-1 (HO-1), we studied HO-1 signaling in CIN. HO-1 levels were increased in CIN; treatment with EGCG further increased HO-1 levels, accompanied by an increase in Nrf2, a regulator of antioxidant proteins. Interestingly, blockade of HO-1 with protoporphyrin IX zinc(II) (ZnPP) prevented the protective effect of EGCG on CIN. ZnPP also blocked the ability of EGCG to increase the activity of an antioxidant (superoxide dismutase), and decrease markers of oxidative stress (myeloperoxidase and malondialdehyde) and inflammation (myeloperoxidase and IL-1β), indicating that HO-1 is the upstream molecule that regulates the EGCG-mediated protection. To determine further the role of HO-1 on the EGCG-mediated inhibition of inflammation, we studied the effect of EGCG on the NLRP3 inflammasome, an upstream signaling of IL-1β. EGCG down-regulated NLRP3 expression, which was blocked by ZnPP, indicating that HO-1 links EGCG with NLRP3. Therefore, EGCG, via up-regulation of HO-1, protects against CIN by amelioration of oxidative stress and inflammation.
authors: Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, P.R. China.|Chongqing Institute of Cardiology, Chongqing Key Laboratory for Hypertension Research, Chongqing, P.R. China.
authors: Zhao
authors: Z
authors: Gao
authors: Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, P.R. China.|Chongqing Institute of Cardiology, Chongqing Key Laboratory for Hypertension Research, Chongqing, P.R. China.
authors: Yu
authors: Y
authors: Han
authors: Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, P.R. China.|Chongqing Institute of Cardiology, Chongqing Key Laboratory for Hypertension Research, Chongqing, P.R. China.
authors: Yunhui
authors: Y
authors: Hu
authors: Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, P.R. China.|Chongqing Institute of Cardiology, Chongqing Key Laboratory for Hypertension Research, Chongqing, P.R. China.
authors: Xiaoyan
authors: X
authors: Wu
authors: Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, P.R. China.|Chongqing Institute of Cardiology, Chongqing Key Laboratory for Hypertension Research, Chongqing, P.R. China.
authors: Yongbin
authors: Y
authors: Wang
authors: Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, P.R. China.|Chongqing Institute of Cardiology, Chongqing Key Laboratory for Hypertension Research, Chongqing, P.R. China.
authors: Xiaoqun
authors: X
authors: Zhang
authors: Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, P.R. China.|Chongqing Institute of Cardiology, Chongqing Key Laboratory for Hypertension Research, Chongqing, P.R. China.
authors: Jinjuan
authors: J
authors: Fu
authors: Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, P.R. China.|Chongqing Institute of Cardiology, Chongqing Key Laboratory for Hypertension Research, Chongqing, P.R. China.
authors: Xue
authors: X
authors: Zou
authors: Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, P.R. China.|Chongqing Institute of Cardiology, Chongqing Key Laboratory for Hypertension Research, Chongqing, P.R. China.
authors: Jun
authors: J
authors: Zhang
authors: Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, P.R. China.|Chongqing Institute of Cardiology, Chongqing Key Laboratory for Hypertension Research, Chongqing, P.R. China.
authors: Xiongwen
authors: X
authors: Chen
authors: Department of Medicine, Division of Renal Disease and Hypertension, The George Washington University School of Medicine & Health Sciences, Washington, DC, United States of America.|Department of Physiology, The George Washington University School of Medicine & Health Sciences, Washington, DC, United States of America.
authors: Pedro A
authors: PA
authors: Jose
authors: Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, P.R. China.|Chongqing Institute of Cardiology, Chongqing Key Laboratory for Hypertension Research, Chongqing, P.R. China.
authors: Xi
authors: X
authors: Lu
authors: Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, P.R. China.|Chongqing Institute of Cardiology, Chongqing Key Laboratory for Hypertension Research, Chongqing, P.R. China.
authors: Chunyu
authors: C
authors: Zeng
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000378:metabolism; D017209:Apoptosis; D002352:Carrier Proteins / Q000378:metabolism / Q000502:physiology; D002392:Catechin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D003287:Contrast Media / Q000009:adverse effects* / Q000737:chemistry; D015536:Down-Regulation; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D020287:In Situ Nick-End Labeling; D058847:Inflammasomes / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D007674:Kidney Diseases / Q000139:chemically induced / Q000188:drug therapy; D008297:Male; D008856:Microscopy, Fluorescence; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D018384:Oxidative Stress; D011524:Protoporphyrins / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D000975:Antioxidants; D002352:Carrier Proteins; D003287:Contrast Media; D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C573346:Nlrp3 protein, rat; D011524:Protoporphyrins; C017803:zinc protoporphyrin; D002392:Catechin; C045651:epigallocatechin gallate; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat