title: Green tea polyphenol (-)-epigallocatechin-3-gallate restores Nrf2 activity and ameliorates crescentic glomerulonephritis.
abstract: Crescentic glomerulonephritis (GN) is the most severe form of GN and is associated with significant morbidity and mortality despite aggressive immunotherapy with steroids, cytotoxic drugs, and plasmapheresis. We examined the therapeutic efficacy of the green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG, 50 mg/kg BW/day x3 weeks), a potent anti-inflammatory and anti-oxidant agent, on experimental crescentic GN induced in 129/svJ mice by administration of rabbit anti-mouse glomerular basement membrane sera. Routine histology and key molecules involved in inflammatory and redox signaling were studied. EGCG treatment significantly reduced mortality, decreased proteinuria and serum creatinine, and markedly improved renal histology when compared with vehicle-treated mice. The improvements in renal function and histology were accompanied by the restoration of Nrf2 signaling (which was impaired in vehicle-treated mice) as shown by increased nuclear translocation of Nrf2 and cytoplasmic glutamate cysteine ligase catalytic subunit, glutamate cysteine ligase modifier subunit, and glutathione peroxidase. EGCG-treated mice also showed reduction in p-Akt, p-JNK, p-ERK1/2 and p-P38 as well as restoration of PPARγ and SIRT1 levels. Lower dose of EGCG (25 mg/kg BW/day x2 weeks) treatment also significantly decreased proteinuria and serum creatinine, and markedly improved renal histology when compared with vehicle-treated mice. Thus, our data illustrate the efficacy of EGCG in reversing the progression of crescentic GN in mice by targeting multiple signaling and inflammatory pathways as well as countering oxidative stress.
authors.affiliation: Department of Clinical Nutrition, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.
authors.forename: Ting
authors.initials: T
authors.lastname: Ye
authors.affiliation: Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America; Department of Pathology, Shandong University School of Medicine, Jinan, Shandong, China.
authors.forename: Junhui
authors.initials: J
authors.lastname: Zhen
authors.affiliation: Department of Biomedical Engineering, University of Houston, Houston, Texas, United States of America; Division of Rheumatology, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.
authors.forename: Yong
authors.initials: Y
authors.lastname: Du
authors.affiliation: Division of Rheumatology, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.
authors.forename: Jason K
authors.initials: JK
authors.lastname: Zhou
authors.affiliation: Center for Nephrology and Clinical Metabolomics, Department of Nephrology & Rheumatology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Ai
authors.initials: A
authors.lastname: Peng
authors.affiliation: Division of Nephrology and Hypertension, University of California Irvine, Irvine, California, United States of America.
authors.forename: Nosratola D
authors.initials: ND
authors.lastname: Vaziri
authors.affiliation: Department of Biomedical Engineering, University of Houston, Houston, Texas, United States of America; Division of Rheumatology, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.
authors.forename: Chandra
authors.initials: C
authors.lastname: Mohan
authors.affiliation: Department of Nephrology, Qingdao University Affiliated Hospital, Qingdao, Shandong, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America; Renal Path Diagnostics, Pathologist BioMedical laboratories, Lewisville, Texas, United States of America; Department of Pathology, Baylor University Medical Center, Dallas, Texas, United States of America.
authors.forename: Xin J
authors.initials: XJ
authors.lastname: Zhou
mesh_terms: D000818:Animals; D000975:Antioxidants; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D005921:Glomerulonephritis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D047495:PPAR gamma / Q000378:metabolism; D015398:Signal Transduction; D056564:Sirtuin 1 / Q000378:metabolism; D013662:Tea / Q000737:chemistry
chemical_list: D000975:Antioxidants; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D047495:PPAR gamma; D013662:Tea; D002392:Catechin; C045651:epigallocatechin gallate; D020928:Mitogen-Activated Protein Kinases; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1