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

Tipoe, George L.; Leung, Tung Ming; Liong, Emily C.; Lau, Thomas Y.H.; Fung, Man Lung; Nanji, Amin A.

doi:10.1016/j.tox.2010.04.014

Cited by 228 publications

(147 citation statements)

References 50 publications

Supporting

Mentioning

138

Contrasting

Order By: Relevance

“…These data indicate that melatonin induces antifibrogenic actions related in part to a lower activation of HSCs during the course of the fibrogenic process. A similar antifibrogenic action, with decreases in the formation of collagen in the liver and in the expression of a-SMA, has been previously reported in rats with CCl 4 liver injury receiving epigallocatechin-3-gallate 6 or after the administration of proanthocyanidins to rats with dimethylnitrosamineinduced liver damage. 9 The role of profibrogenic cytokines is central for the development of fibrosis, with progression greatly dependent on the production of TGF-b, which is the master cytokine in liver fibrogenesis and one of the primary targets in the development of antifibrotic agents.…”

Section: Discussionsupporting

confidence: 81%

“…9 The role of profibrogenic cytokines is central for the development of fibrosis, with progression greatly dependent on the production of TGF-b, which is the master cytokine in liver fibrogenesis and one of the primary targets in the development of antifibrotic agents. 29 TGF-b is downregulated in animal models of fibrosis by treatment with curcumin, 30 epigallocatechin-3-gallate, 6 or polyprenols. 7 Present data confirm that melatonin also decreases TGF-b expression in CCl 4 -treated mice, a fact that undoubtedly contributes to the interference of the indol with the activation of HSCs.…”

Section: Discussionmentioning

confidence: 99%

“…Oxidative stress aggravates liver fibrosis. 5 Thus, inhibiting oxidative stress has been considered a potential useful strategy to prevent the development of hepatic fibrogenesis, and it has been reported that antioxidants such as epigallocatechin-3-gallate, 6 polyprenols, 7 quercetin, 8 or proanthocyanidin, 9 among others, may prevent liver injury in different animal models of fibrosis.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Melatonin limits the expression of profibrogenic genes and ameliorates the progression of hepatic fibrosis in mice

Crespo

San‐Miguel

Fernández

et al. 2015

Translational Research

View full text Add to dashboard Cite

We investigated whether melatonin ameliorates fibrosis and limits the expression of fibrogenic genes in mice treated with carbon tetrachloride (CCl 4 ). Mice in treatment groups received CCl 4 5 mL/g body weight intraperitoneally twice a week for 4 or 6 weeks. Melatonin was given at 5 or 10 mg/kg/d intraperitoneally, beginning 2 weeks after the start of CCl 4 administration. Treatment with CCl 4 resulted in fibrosis evidenced by the staining of Van Gieson and a-smooth muscle actin (a-SMA) positive cells in the liver. At both 4 and 6 weeks, CCl 4 induced an increase in the messenger RNA levels of collagens I and III, transforming growth factor (TGF)-b, platelet-derived growth factor (PDGF), connective tissue growth factor (CTGF), amphiregulin, matrix metalloproteinase (MMP)-9, and tissue inhibitor of metalloproteinase (TIMP)-1. Protein concentrations of CTGF, amphiregulin, MMP-9, TIMP-1, and phospho-Smad3 were also significantly augmented in fibrotic mice. Melatonin successfully attenuated liver injury, as shown by histopathology and decreased levels of serum transaminases. Immunohistochemical staining of a-SMA indicated an abrogation of hepatic stellate cell activation by the indol. Furthermore, melatonin treatment resulted in significant inhibition of the expression of collagens I and III, TGF-b, PDGF, CTGF, amphiregulin, and phospho-Smad3. The MMP-9 activity decreased and the expression of nuclear factor erythroid-2-related factor 2 (Nrf2) increased in mice receiving melatonin. Data obtained suggest that attenuation of multiple profibrogenic gene pathways contributes to the beneficial effects of melatonin in mice with CCl 4 -induced liver fibrosis. (Translational Research 2015;165:346-357) Abbreviations: a-SMA ¼ a-smooth muscle actin; CCl 4 ¼ carbon tetrachloride; CTGF ¼ connective tissue growth factor; HSC ¼ hepatic stellate cell; MMP-9 ¼ matrix metalloproteinase 9; Nrf2 ¼ nuclear factor erythroid 2-related factor 2; PDGF ¼ platelet-derived growth factor; TGF-b ¼ transforming growth factor b; TIMP-1 ¼ tissue inhibitor of metalloproteinase 1 H epatic fibrosis is a reversible wound-healing response to either acute or chronic cellular injury from a wide variety of etiologies, characterized by an excessive deposition of extracellular matrix (ECM) resulting in liver dysfunction and irreversible cirrhosis. During liver fibrogenesis, hepatic stellate cells (HSCs) undergo activation to a a-smooth muscle actin (SMA)-positive myofibroblastic phenotype and synthesize excess ECM components, particularly collagen. 1 Among the numerous From the

show abstract

Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Melatonin limits the expression of profibrogenic genes and ameliorates the progression of hepatic fibrosis in mice

Crespo

San‐Miguel

Fernández

et al. 2015

Translational Research

View full text Add to dashboard Cite

show abstract

“…Carbon tetrachloride (CCl 4 ) poisoning is one of the most commonly used models of acute liver damage. The hepatotoxic effects of CCl 4 were attributed to the excessive production of free radicals [2] . Previous studies have shown that natural compounds with antioxidant activity could ameliorate CCl 4 -induced liver damage, thus preventing acute liver failure [3,4] .…”

Section: Introductionmentioning

confidence: 99%

Differential hepatoprotective mechanisms of rutin and quercetin in CCl4-intoxicated BALB/cN mice

et al. 2012

View full text Add to dashboard Cite

Aim: To investigate the mechanisms underlying the protective effects of quercetin-rutinoside (rutin) and its aglycone quercetin against CCl 4 -induced liver damage in mice. Methods: BALB/cN mice were intraperitoneally administered rutin (10, 50, and 150 mg/kg) or quercetin (50 mg/kg) once daily for 5 consecutive days, followed by the intraperitoneal injection of CCl 4 in olive oil (2 mL/kg, 10% v/v). The animals were sacrificed 24 h later. Blood was collected for measuring the activities of ALT and AST, and the liver was excised for assessing Cu/Zn superoxide dismutase (SOD) activity, GSH and protein concentrations and also for immunoblotting. Portions of the livers were used for histology and immunohistochemistry. Results: Pretreatment with rutin and, to a lesser extent, with quercetin significantly reduced the activity of plasma transaminases and improved the histological signs of acute liver damage in CCl 4 -intoxicated mice. Quercetin prevented the decrease in Cu/Zn SOD activity in CCl 4 -intoxicated mice more potently than rutin. However, it was less effective in the suppression of nitrotyrosine formation. Quercetin and, to a lesser extent, rutin attenuated the inflammation in the liver by down-regulating the CCl 4 -induced activation of nuclear factor-kappa B (NF-κB), tumor necrosis factor-α (TNF-α) and cyclooxygenase (COX-2). The expression of inducible nitric oxide synthase (iNOS) was more potently suppressed by rutin than by quercetin. Treatment with both flavonoids significantly increased NF-E2-related factor 2 (Nrf2) and heme oxygenase (HO-1) expression in injured livers, although quercetin was less effective than rutin at an equivalent dose. Quercetin more potently suppressed the expression of transforming growth factor-β1 (TGF-β1) than rutin. Conclusion: Rutin exerts stronger protection against nitrosative stress and hepatocellular damage but has weaker antioxidant and antiinflammatory activities and antifibrotic potential than quercetin, which may be attributed to the presence of a rutinoside moiety in position 3 of the C ring.

show abstract

“…Recent studies have shown that different types of gallic acid-derived constituents inhibit various infl ammatory mediators, including cyclooxygenase-2, TNF-α and iNOS (Lin and Lin, 1997;Jung et al, 2010;Tipoe et al, 2010). It would be interesting to examine inhibitory effects of EDG and other gallic acid-derived components on infl ammatory responses in vivo, which produce valuable information about what component would be the most effective for the treatment of infl ammation-associated diseases.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Nitric Oxide Production by Ethyl Digallates Isolated from Galla Rhois in RAW 264.7 Macrophages

Park¹,

Hur²,

Lee³

et al. 2011

Biomolecules and Therapeutics

View full text Add to dashboard Cite

Galla Rhois and its components are known to possess anti-infl ammatory properties. In the present study, we prepared equilibrium mixture of ethyl m-digallate and ethyl p-digallate isomers (EDG) from Galla Rhois and examined its effect on nitric oxide (NO) production in murine macrophage cell line. Treatment of RAW264.7 macrophages with EDG signifi cantly inhibited NO production and inducible nitric oxide synthase (iNOS) expression stimulated by LPS, as assessed by Western blot and quantitative RT-PCR analyses. We also demonstrated that EDG treatment led to an increase in heme oxygenase-1 (HO-1) mRNA and protein expression. EDG treatment also enhanced expression level of nuclear factor-erythroid 2-related factor 2 (Nrf2) in nucleus, which is critical for transcriptional induction of HO-1. Treatment with SnPP (tin protoporphyrin IX), a selective HO-1 inhibitor, reversed EDG-mediated inhibition of nitrite production, suggesting that HO-1 plays an important role in the suppression of NO production by EDG. Taken together, these results indicate that EDG isolated from Galla Rhois suppresses LPS-stimulated NO production in RAW 264.7 macrophages via HO-1 induction.

show abstract

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

Cited by 228 publications

References 50 publications

Melatonin limits the expression of profibrogenic genes and ameliorates the progression of hepatic fibrosis in mice

Melatonin limits the expression of profibrogenic genes and ameliorates the progression of hepatic fibrosis in mice

Differential hepatoprotective mechanisms of rutin and quercetin in CCl4-intoxicated BALB/cN mice

Inhibition of Nitric Oxide Production by Ethyl Digallates Isolated from Galla Rhois in RAW 264.7 Macrophages

Contact Info

Product

Resources

About