Epigallocatechin-3-gallate (EGCG) reduces liver inflammation, oxidative stress and fibrosis in carbon tetrachloride (CCl₄)-induced liver injury in mice

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• 作者：George L. Tipoe ; Tung Ming Leung ; Emily C. Liong ; Thomas Yue Huen Lau ; Man Lung Fung ; Amin A. Nanji
• 关键词：Epigallocatechin-3-gallate (EGCG) ; Liver inflammation ; Oxidative stress ; Liver fibrosis ; Carbon tetrachloride (CCl₄)
• 刊名：Toxicology
• 出版年：2010
• 出版时间：29 June 2010
• 年：2010
• 卷：273
• 期：1-3
• 页码：45-52
• 全文大小：1401 K

文摘

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 CCl₄ 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-α, COX-2, iNOS, α-smooth muscle actin (α-SMA), transforming growth factor (TGF-β₁), 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-κB and the expression level of C/EBP were also assessed. Chronic CCl₄ 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-κB 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 α-SMA and all of the assayed pro-fibrogenic markers except TIMP-2 and MMP-9. EGCG significantly attenuated the severity of CCl₄-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.