Epigallocatechin-3-gallate (EGCG) reduces liver inflammation, oxidative stress and fibrosis in carbon tetrachloride (CCl4)-induced liver injury in mice.
The anti-inflammatory and antioxidant effects of epigallocatechin-3-gallate (EGCG) are considered important forces in attenuate liver injury and fibrosis. The aim of the study was to investigate the effect of EGCG on the expression of fibrogenic factors and whether EGCG attenuates the severity of oxidative stress and inflammatory response in chronic liver injury. Mice were administered with CCl(4) together with or without EGCG for 8 weeks (n=6-8 per group). Histopathological and biochemical analyses were carried out. The mRNA expression levels of TNF-alpha, COX-2, iNOS, alpha-smooth muscle actin (alpha-SMA), transforming growth factor (TGF-beta(1)), pro-collagen-I, matrix metalloproteinases (MMP-2, -9) and their inhibitors (TIMP-1, -2) were determined by RT-PCR. The collagen deposited in the liver was detected by Sirius Red staining. The formation of nitrotyrosine was measured as a marker of oxidative stress. The activity level of NF-kappaB and the expression level of C/EBP were also assessed. Chronic CCl(4) treatment caused liver injury, oxidative stress and nitrosative stress, and collagen accumulation in the liver. The expression levels of pro-inflammatory and pro-fibrotic mediators and the activity of NF-kappaB were increased. Treatment with EGCG significantly reduced liver injury, oxidative stress and the inflammatory response. EGCG also significantly reduced the formation of collagen in the liver, the expression of alpha-SMA and all of the assayed pro-fibrogenic markers except TIMP-2 and MMP-9. EGCG significantly attenuated the severity of CCl(4)-induced liver injury and the progression of liver fibrosis. The protective effect of EGCG may in part be a consequence of the reduction in oxidative stress and the pro-inflammatory response.
Tipoe
George L
GL
Department of Anatomy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, SAR. tgeorge@hkucc.hku.hk
Leung
Tung Ming
TM
Liong
Emily C
EC
Lau
Thomas Yue Huen
TY
Fung
Man Lung
ML
Nanji
Amin A
AA
D000199:Actins / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D002251:Carbon Tetrachloride; D002392:Catechin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000378:metabolism; D024042:Collagen Type I / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000378:metabolism; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D000199:Actins; D000893:Anti-Inflammatory Agents; D024042:Collagen Type I; D052246:Cyclooxygenase 2 Inhibitors; D019714:Tissue Inhibitor of Metalloproteinases; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; C544013:alpha-smooth muscle actin, mouse; C002744:3-nitrotyrosine; D014443:Tyrosine; D002392:Catechin; C045651:epigallocatechin gallate; D002251:Carbon Tetrachloride; D052247:Nitric Oxide Synthase Type II; D020782:Matrix Metalloproteinases