Green Tea Polyphenol (-)-Epigallocatechin-3-Gallate (EGCG) Ameliorates Experimental Immune-Mediated Glomerulonephritis.
Ting Ye, Ai Peng, Dinesh Rakheja, Chandra Mohan, Xin J Zhou. UT Southwestern Medical Center, Dallas, TX
Background: Oxidative stress and inflammation play critical roles in the pathogenesis of immune-mediated glomerulonephritis (GN). The green tea catechins, particularly (-)-epigallocatechin-3-gallate (EGCG), are potent anti-inflammatory and anti-oxidant agents shown to inhibit leukocyte chemotaxis, quench free radicals, chelate transition metals, and interrupt lipid peroxidation chain reaction. It is estimated that EGCG is 25 times more potent than vitamin E and 100 times more potent than vitamin C making it an attractive compound for the treatment of diseases such as anti-GBM-GN that are characterized by severe immunologic and oxidative injury. However, the effect of EGCG on the clinical and pathological progression of immune-mediated renal injury has not been investigated.
Design: We tested the hypothesis that the anti-inflammatory and anti-oxidant properties of EGCG may favorably affect the course of immune-mediated GN using a murine model of anti-GBM-GN. 129/svJ mice were challenged with rabbit anti-mouse-GBM sera to induce GN and subsequently divided into EGCG (50 mg/kg/day, orally) and vehicle treated groups. Routine histology, markers of oxidative stress and key molecules associated with redox and inflammatory pathways were studied.
Results: Vehicle-treated mice developed glomerular crescents, tubulointerstitial disease and inflammatory cell infiltrates. EGCG treatment led to reduced proteinuria and serum creatinine and marked improvement in renal histology. Vehicle-treated mice showed increased oxidative stress [malondialdehyde (MDA), H2O2 and nitrotyrosine], elevated osteopontin (OPN), p65-NFκB, inducible nitric oxide synthase (iNOS), NO metabolites, superoxide dismutase (SOD), myeloperoxidase (MPO), p-Akt, and p47phox, and reduced PPARγ, glutathione peroxidase (GPx), and catalase activity. Treatment with EGCG led to a reduction in oxidative stress, normalization of OPN, p65-NFκB, iNOS, NO metabolites, p-Akt, p47phox, MPO, GPx, and PPARγ, and a significant increase in SOD expression.
Conclusions: our data suggest that EGCG ameliorates laboratory and histologic abnormalities in the mouse model of immune-mediated GN. These salutary effects of EGCG are likely mediated by the anti-inflammatory and anti-oxidative properties of this compound. These observations demonstrate the potential utility of EGCG as a novel therapeutic agent for the treatment of immune-mediated glomerulonephritides and various other immune-mediated diseases.
Category: Kidney (does not include tumors)
Wednesday, March 2, 2011 1:00 PM
Poster Session VI # 262, Wednesday Afternoon