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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

Renal histology of normal control mice, vehicle-treated mice with anti-GBM-GN, and EGCG-treated mice with anti-GBM-GN.Kidneys from mice 4 weeks after induction of anti-GBM-GN with or without EGCG treatment and kidneys from normal control mice were evaluated by light microscopy. In the PAS stained sections, the kidneys in the vehicle-treated mice revealed severe glomerular hypercellularity with large crescents. There were also significant tubular atrophy and interstitial fibrosis with prominent interstitial inflammatory infiltrates (original magnification x 400). In contrast, the EGCG-treated animals exhibited mild to moderate glomerular injury with minimal crescent formation and focal mild tubulointerstitial injury. No significant histopathologic changes were observed in the normal control mice. The bar graphs represent semi-quantification of glomerular in jury (GN score), crescent formation and tubulointerstitial injury (TI score). Values are mean ± SEM.; n = 8–10 in each group.
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pone.0119543.g001: Renal histology of normal control mice, vehicle-treated mice with anti-GBM-GN, and EGCG-treated mice with anti-GBM-GN.Kidneys from mice 4 weeks after induction of anti-GBM-GN with or without EGCG treatment and kidneys from normal control mice were evaluated by light microscopy. In the PAS stained sections, the kidneys in the vehicle-treated mice revealed severe glomerular hypercellularity with large crescents. There were also significant tubular atrophy and interstitial fibrosis with prominent interstitial inflammatory infiltrates (original magnification x 400). In contrast, the EGCG-treated animals exhibited mild to moderate glomerular injury with minimal crescent formation and focal mild tubulointerstitial injury. No significant histopathologic changes were observed in the normal control mice. The bar graphs represent semi-quantification of glomerular in jury (GN score), crescent formation and tubulointerstitial injury (TI score). Values are mean ± SEM.; n = 8–10 in each group.

Mentions: The vehicle-treated mice showed moderate to severe renal injury characterized by crescent formation with significant intracapillary hypercellularity, obliterated capillary lumens, and thickened capillary walls. Tubular atrophy and dilation with hyaline casts and interstitial fibrosis were also noted. In comparison, the EGCG-treated mice exhibited milder renal injury with only occasional crescent formation and focal tubulointerstitial injury (Figs. 1 and 2). No lesions were seen in the normal control group. In addition, the vehicle-treated mice showed heavy glomerular and interstitial infiltrations by macrophages and lymphocytes, which was significantly attenuated by EGCG administration (Figs. 1 and 2). Thus, the severe renal lesions and heavy inflammation associated with anti-GBM disease were greatly reduced in by EGCG administration.


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)

Renal histology of normal control mice, vehicle-treated mice with anti-GBM-GN, and EGCG-treated mice with anti-GBM-GN.Kidneys from mice 4 weeks after induction of anti-GBM-GN with or without EGCG treatment and kidneys from normal control mice were evaluated by light microscopy. In the PAS stained sections, the kidneys in the vehicle-treated mice revealed severe glomerular hypercellularity with large crescents. There were also significant tubular atrophy and interstitial fibrosis with prominent interstitial inflammatory infiltrates (original magnification x 400). In contrast, the EGCG-treated animals exhibited mild to moderate glomerular injury with minimal crescent formation and focal mild tubulointerstitial injury. No significant histopathologic changes were observed in the normal control mice. The bar graphs represent semi-quantification of glomerular in jury (GN score), crescent formation and tubulointerstitial injury (TI score). Values are mean ± SEM.; n = 8–10 in each group.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4364748&req=5

pone.0119543.g001: Renal histology of normal control mice, vehicle-treated mice with anti-GBM-GN, and EGCG-treated mice with anti-GBM-GN.Kidneys from mice 4 weeks after induction of anti-GBM-GN with or without EGCG treatment and kidneys from normal control mice were evaluated by light microscopy. In the PAS stained sections, the kidneys in the vehicle-treated mice revealed severe glomerular hypercellularity with large crescents. There were also significant tubular atrophy and interstitial fibrosis with prominent interstitial inflammatory infiltrates (original magnification x 400). In contrast, the EGCG-treated animals exhibited mild to moderate glomerular injury with minimal crescent formation and focal mild tubulointerstitial injury. No significant histopathologic changes were observed in the normal control mice. The bar graphs represent semi-quantification of glomerular in jury (GN score), crescent formation and tubulointerstitial injury (TI score). Values are mean ± SEM.; n = 8–10 in each group.
Mentions: The vehicle-treated mice showed moderate to severe renal injury characterized by crescent formation with significant intracapillary hypercellularity, obliterated capillary lumens, and thickened capillary walls. Tubular atrophy and dilation with hyaline casts and interstitial fibrosis were also noted. In comparison, the EGCG-treated mice exhibited milder renal injury with only occasional crescent formation and focal tubulointerstitial injury (Figs. 1 and 2). No lesions were seen in the normal control group. In addition, the vehicle-treated mice showed heavy glomerular and interstitial infiltrations by macrophages and lymphocytes, which was significantly attenuated by EGCG administration (Figs. 1 and 2). Thus, the severe renal lesions and heavy inflammation associated with anti-GBM disease were greatly reduced in by EGCG administration.

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