title: The green tea polyphenol (-)-epigallocatechin-3-gallate ameliorates experimental immune-mediated glomerulonephritis.
abstract: The unchecked overproduction of reactive oxygen and nitrogen species by inflammatory cells can cause tissue damage, intensify inflammation, promote apoptosis, and accelerate the progression of immune-mediated glomerulonephritis (GN). Here we tested whether the anti-inflammatory and antioxidant properties of the green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) favorably affect the development of immune-mediated GN. Pretreatment of 129/svJ mice with EGCG from 2 days before to 2 weeks after the induction of GN led to reduced proteinuria and serum creatinine, and marked improvement in renal histology when compared with vehicle-pretreated diseased mice. This pretreatment reduced oxidative stress, and normalized osteopontin, p65/nuclear factor-κB, inducible nitric oxide synthase, nitric oxide metabolites, p-Akt, phosphorylated extracellular signal-regulated kinases 1 and 2, p47phox, and myeloperoxidase, all of which were elevated in vehicle-pretreated diseased mice. Levels of glutathione peroxidase and peroxisome proliferator-activated receptor-γ (PPARγ), both reduced in the vehicle-pretreated diseased mice, were normalized. This renoprotective effect was reversed by concomitant administration of the PPARγ antagonist GW9662 throughout the EGCG pretreatment period. Importantly, mortality and renal dysfunction were significantly attenuated even when the polyphenol treatment was initiated 1 week after the onset of GN. Thus, EGCG reversed the progression of immune-mediated GN in mice by targeting redox and inflammatory pathways.
authors.affiliation: Department of Nephrology, Shanghai Tenth People's Hospital of Tongji University, Shanghai, China.
authors.forename: Ai
authors.initials: A
authors.lastname: Peng
authors.forename: Ting
authors.initials: T
authors.lastname: Ye
authors.forename: Dinesh
authors.initials: D
authors.lastname: Rakheja
authors.forename: Yangke
authors.initials: Y
authors.lastname: Tu
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Yong
authors.initials: Y
authors.lastname: Du
authors.forename: Jason K
authors.initials: JK
authors.lastname: Zhou
authors.forename: Nosratola D
authors.initials: ND
authors.lastname: Vaziri
authors.forename: Zhao
authors.initials: Z
authors.lastname: Hu
authors.forename: Chandra
authors.initials: C
authors.lastname: Mohan
authors.forename: Xin J
authors.initials: XJ
authors.lastname: Zhou
mesh_terms: D000818:Animals; D019867:Anti-Glomerular Basement Membrane Disease / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D007668:Kidney / Q000473:pathology; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D053495:Osteopontin / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D047495:PPAR gamma / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013662:Tea / Q000737:chemistry*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D016328:NF-kappa B; D047495:PPAR gamma; C506896:Spp1 protein, mouse; D013662:Tea; D053495:Osteopontin; D009569:Nitric Oxide; D002392:Catechin; C045651:epigallocatechin gallate