TY - JOUR
T1 - The green tea polyphenol ()-epigallocatechin-3-gallate ameliorates experimental immune-mediated glomerulonephritis
AU - Peng, Ai
AU - Ye, Ting
AU - Rakheja, Dinesh
AU - Tu, Yangke
AU - Wang, Tao
AU - Du, Yong
AU - Zhou, Jason K.
AU - Vaziri, Nosratola D.
AU - Hu, Zhao
AU - Mohan, Chandra
AU - Zhou, Xin J.
N1 - Funding Information:
This work was supported in part by grants from the NIH (R21 AT004436), the National Natural Science Foundation of China (30472163 and 30871202), the High Technology Research and Development Program of China (2009AA02Z416), and by funds from the Drs George and Anne Race Distinguished Professorship in Pathology. Part of this work was presented at the annual meeting of the United States and Canadian Academy of Pathology in San Antonio, Texas, in March 2011.
PY - 2011/9/2
Y1 - 2011/9/2
N2 - 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-B, 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.
AB - 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-B, 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.
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U2 - 10.1038/ki.2011.121
DO - 10.1038/ki.2011.121
M3 - Article
C2 - 21544063
AN - SCOPUS:80052269190
SN - 0085-2538
VL - 80
SP - 601
EP - 611
JO - Kidney International
JF - Kidney International
IS - 6
ER -