title: Epigallocatechin-3-gallate protects kidneys from ischemia reperfusion injury by HO-1 upregulation and inhibition of macrophage infiltration.
abstract: Epigallocatechin-3-gallate (EGCG) shows diverse chemical and biological activities. We investigated the effects of EGCG in a rat renal ischemia reperfusion (I/R) injury model. Sprague-Dawley rats received intraperitoneal injection of 50 mg/kg EGCG 48 h, 24 h, and 30 min prior to I/R injury. The animals were subjected to left renal occlusion for 45 min. EGCG treatment suppressed the peak in serum creatinine. EGCG-treated kidneys showed significantly less tubular damage and a decreased number of apoptotic cells. The I/R-induced elevation in the renal MDA level was significantly decreased in the EGCG group. Reverse-transcriptase polymerase chain reaction showed that EGCG significantly decreased the expression of MHC class II, TLR2, TLR4, MCP-1, IL-18, TGF-β1, procollagen Ia1, TIMP-1, and Kim-1. ED-1 staining showed reduced macrophage infiltration and α-SMA staining revealed less interstitial expression. Heme oxygenase-1 (HO-1) expression in I/R kidneys was upregulated in the EGCG group based on the results of both RT-PCR and Western blotting analysis. Blockade of HO-1 gene induction by SnPP increased renal tubular damage and macrophage infiltration. These findings suggest that EGCG protects the kidneys against I/R injury by reducing macrophage infiltration and decreasing renal fibrosis. These beneficial effects may be mediated, in part, by augmentation of the HO-1 gene.
authors.affiliation: Department of Urology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Kakuta
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Okumi
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Isaka
authors.forename: Koichi
authors.initials: K
authors.lastname: Tsutahara
authors.forename: Toyofumi
authors.initials: T
authors.lastname: Abe
authors.forename: Koji
authors.initials: K
authors.lastname: Yazawa
authors.forename: Naotsugu
authors.initials: N
authors.lastname: Ichimaru
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Matsumura
authors.forename: Suong-Hyu
authors.initials: SH
authors.lastname: Hyon
authors.forename: Shiro
authors.initials: S
authors.lastname: Takahara
authors.forename: Norio
authors.initials: N
authors.lastname: Nonomura
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D052160:Benzothiazoles; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D003959:Diamines; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects* / Q000196:embryology; D015227:Lipid Peroxidation; D008264:Macrophages / Q000378:metabolism*; D008315:Malondialdehyde / Q000378:metabolism; D009130:Muscle, Smooth / Q000378:metabolism; D009930:Organic Chemicals / Q000494:pharmacology; D011804:Quinolines; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
chemical_list: D000199:Actins; D052160:Benzothiazoles; D003959:Diamines; D009930:Organic Chemicals; D011804:Quinolines; C098022:SYBR Green I; D008315:Malondialdehyde; D002392:Catechin; C045651:epigallocatechin gallate; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat