title: Epigallocatechin gallate suppresses peritoneal fibrosis in mice.
abstract: Long-term peritoneal dialysis (PD) leads to histological changes in the peritoneal membrane. Angiogenesis and inflammation caused by glucose degradation products (GDPs) play crucial roles in peritoneal fibrosis. One such GDP is methylglyoxal (MGO), which enhances the formation of advanced glycation end products (AGEs). AGEs bind to their receptor (RAGE) and activate nuclear factor-κB (NF-κB), which is a key regulator of angiogenesis and inflammation. Recent studies have indicated that (-)-epigallocatechin gallate (EGCG), a tea polyphenol, inhibits angiogenesis and inflammation. Here, we examined whether EGCG suppresses peritoneal fibrosis in mice. Based on preliminary examination, 2mL of 40mM MGO or PD fluid was injected intraperitoneally and EGCG (50mg/kg) or saline was injected subcutaneously for 3weeks. In comparison to PD fluid+saline-treated mice, the peritoneal tissues of MGO+saline-treated mice showed marked thickening of the submesothelial compact zone. In the submesothelial compact zone of the MGO+saline-treated mice, CD31-positive vessels and vascular endothelial growth factor-positive cells were significantly increased, as were inflammation, F4/80-positive macrophages, and monocyte chemotactic protein-1. Moreover, 8-hydroxydeoxyguanosine, a marker of reactive oxygen species, and NF-κB, determined by Southwestern histochemistry, in the submesothelial compact zone were also increased in MGO+saline-treated mice. These changes were attenuated in MGO+EGCG-treated mice. We demonstrated that EGCG treatment suppresses peritoneal fibrosis via inhibition of NF-κB. Furthermore, EGCG inhibits reactive oxygen species production. The results of this study indicate that EGCG is a potentially novel candidate for the treatment of peritoneal fibrosis.
authors.affiliation: Second Department of Internal Medicine, Nagasaki University School of Medicine, Japan.
authors.forename: Mineaki
authors.initials: M
authors.lastname: Kitamura
authors.forename: Tomoya
authors.initials: T
authors.lastname: Nishino
authors.forename: Yoko
authors.initials: Y
authors.lastname: Obata
authors.forename: Akira
authors.initials: A
authors.lastname: Furusu
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Hishikawa
authors.forename: Takehiko
authors.initials: T
authors.lastname: Koji
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kohno
mesh_terms: D000818:Animals; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D018932:Chemokine CCL2 / Q000378:metabolism; D015314:Dialysis Solutions / Q000494:pharmacology; D007249:Inflammation / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D056627:Peritoneal Fibrosis / Q000188:drug therapy / Q000473:pathology*; D010537:Peritoneum / Q000098:blood supply / Q000187:drug effects; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011765:Pyruvaldehyde / Q000633:toxicity; D017382:Reactive Oxygen Species / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D018932:Chemokine CCL2; D015314:Dialysis Solutions; D016328:NF-kappa B; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D017382:Reactive Oxygen Species; D042461:Vascular Endothelial Growth Factor A; D011765:Pyruvaldehyde; D002392:Catechin; C045651:epigallocatechin gallate