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Green tea polyphenol (-)-epigallocatechin-3-gallate restores Nrf2 activity and ameliorates crescentic glomerulonephritis.

Ye T, Zhen J, Du Y, Zhou JK, Peng A, Vaziri ND, Mohan C, Xu Y, Zhou XJ - PLoS ONE (2015)

Bottom Line: EGCG treatment significantly reduced mortality, decreased proteinuria and serum creatinine, and markedly improved renal histology when compared with vehicle-treated mice.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.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus

Western Blot analyses of SIRT1 and PPARγ in kidneys of normal control mice, vehicle-treated mice with anti-GBM-GN, and EGCG-treated mice with anti-GBM-GN.Western blot showed significant reduction in the levels of SIRT1 and PPARγ in vehicle-treated mice with anti-GMB-GN, compared to the levels in normal control mice. EGCG treatment of mice with anti-GBM-GN led to significant increase in the levels of SIRT1 and PPARγ. Values are expressed as mean ± SEM; n = 8–10 in each group.
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pone.0119543.g007: Western Blot analyses of SIRT1 and PPARγ in kidneys of normal control mice, vehicle-treated mice with anti-GBM-GN, and EGCG-treated mice with anti-GBM-GN.Western blot showed significant reduction in the levels of SIRT1 and PPARγ in vehicle-treated mice with anti-GMB-GN, compared to the levels in normal control mice. EGCG treatment of mice with anti-GBM-GN led to significant increase in the levels of SIRT1 and PPARγ. Values are expressed as mean ± SEM; n = 8–10 in each group.

Mentions: Compared with the normal control group, the vehicle treated anti-GBM-GN mice showed significant reduction of PPARγ and SIRT1 in the kidney tissue. EGCG administration reversed these changes (Fig. 7). Thus, by activating PPARr (an anti-inflammatory transcription factor), EGCG reduces inflammation and by restoring SIRT1 level, EGCG facilitates tissue repair and regeneration.


Green tea polyphenol (-)-epigallocatechin-3-gallate restores Nrf2 activity and ameliorates crescentic glomerulonephritis.

Ye T, Zhen J, Du Y, Zhou JK, Peng A, Vaziri ND, Mohan C, Xu Y, Zhou XJ - PLoS ONE (2015)

Western Blot analyses of SIRT1 and PPARγ in kidneys of normal control mice, vehicle-treated mice with anti-GBM-GN, and EGCG-treated mice with anti-GBM-GN.Western blot showed significant reduction in the levels of SIRT1 and PPARγ in vehicle-treated mice with anti-GMB-GN, compared to the levels in normal control mice. EGCG treatment of mice with anti-GBM-GN led to significant increase in the levels of SIRT1 and PPARγ. Values are expressed as mean ± SEM; n = 8–10 in each group.
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Related In: Results  -  Collection

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pone.0119543.g007: Western Blot analyses of SIRT1 and PPARγ in kidneys of normal control mice, vehicle-treated mice with anti-GBM-GN, and EGCG-treated mice with anti-GBM-GN.Western blot showed significant reduction in the levels of SIRT1 and PPARγ in vehicle-treated mice with anti-GMB-GN, compared to the levels in normal control mice. EGCG treatment of mice with anti-GBM-GN led to significant increase in the levels of SIRT1 and PPARγ. Values are expressed as mean ± SEM; n = 8–10 in each group.
Mentions: Compared with the normal control group, the vehicle treated anti-GBM-GN mice showed significant reduction of PPARγ and SIRT1 in the kidney tissue. EGCG administration reversed these changes (Fig. 7). Thus, by activating PPARr (an anti-inflammatory transcription factor), EGCG reduces inflammation and by restoring SIRT1 level, EGCG facilitates tissue repair and regeneration.

Bottom Line: EGCG treatment significantly reduced mortality, decreased proteinuria and serum creatinine, and markedly improved renal histology when compared with vehicle-treated mice.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.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus