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Research ArticleArticle

Curcumin Protects the Rat Liver from CCl4-Caused Injury and Fibrogenesis by Attenuating Oxidative Stress and Suppressing Inflammation

Yumei Fu, Shizhong Zheng, Jianguo Lin, Jan Ryerse and Anping Chen
Molecular Pharmacology February 2008, 73 (2) 399-409; DOI: https://doi.org/10.1124/mol.107.039818
Yumei Fu
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Shizhong Zheng
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Jianguo Lin
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Jan Ryerse
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Anping Chen
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Abstract

We previously demonstrated that curcumin, a polyphenolic antioxidant purified from turmeric, up-regulated peroxisome proliferator-activated receptor (PPAR)-γ gene expression and stimulated its signaling, leading to the inhibition of activation of hepatic stellate cells (HSC) in vitro. The current study evaluates the in vivo role of curcumin in protecting the liver against injury and fibrogenesis caused by carbon tetrachloride (CCl4) in rats and further explores the underlying mechanisms. We hypothesize that curcumin might protect the liver from CCl4-caused injury and fibrogenesis by attenuating oxidative stress, suppressing inflammation, and inhibiting activation of HSC. This report demonstrates that curcumin significantly protects the liver from injury by reducing the activities of serum aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase, and by improving the histological architecture of the liver. In addition, curcumin attenuates oxidative stress by increasing the content of hepatic glutathione, leading to the reduction in the level of lipid hydroperoxide. Curcumin dramatically suppresses inflammation by reducing levels of inflammatory cytokines, including interferon-γ, tumor necrosis factor-α, and interleukin-6. Furthermore, curcumin inhibits HSC activation by elevating the level of PPARγ and reducing the abundance of platelet-derived growth factor, transforming growth factor-β, their receptors, and type I collagen. This study demonstrates that curcumin protects the rat liver from CCl4-caused injury and fibrogenesis by suppressing hepatic inflammation, attenuating hepatic oxidative stress and inhibiting HSC activation. These results confirm and extend our prior in vitro observations and provide novel insights into the mechanisms of curcumin in the protection of the liver. Our results suggest that curcumin might be a therapeutic antifibrotic agent for the treatment of hepatic fibrosis.

Footnotes

  • This work was supported by National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases grant R01-DK047995 (to A.C.).

  • Y.F. and S.Z. made equal contributions to this work.

  • ABBREVIATIONS: ECM, extracellular matrix; HSC, hepatic stellate cell(s); PDGF, platelet-derived growth factor; TGF, transforming growth factor; PDGFR, platelet-derived growth factor receptor; Tβ-RI, type I receptor for transforming growth factor-β; Tβ-RII, type II receptor for transforming growth factor-β; EGFR, epidermal growth factor receptor; PPAR, peroxisome proliferator-activated receptor; AST, aspartate aminotransferase; ALT, alanine aminotransferase; ALP, and alkaline phosphatase; ELISA, enzyme-linked immunosorbent assay; IFN, interferon; TNF, tumor necrosis factor; IL, interleukin; RT, room temperature; GSH, glutathione; GSSG, oxidized glutathione; MES, 2-(N-morpholino)ethanesulfonic acid; LPO, lipid peroxidation; PCR, polymerase chain reaction; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; SMA, smooth muscle actin; GCL, glutamate-cysteine ligase; cGCL, heavy catalytic subunit of glutamate-cysteine ligase (73 kDa); mGCL, light regulatory subunit of glutamate-cysteine ligase (31 kDa); IHC, immunohistochemical/immunohistochemistry.

    • Received July 9, 2007.
    • Accepted November 9, 2007.
  • The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 73 (2)
Molecular Pharmacology
Vol. 73, Issue 2
1 Feb 2008
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Research ArticleArticle

Curcumin Protects the Rat Liver from CCl4-Caused Injury and Fibrogenesis by Attenuating Oxidative Stress and Suppressing Inflammation

Yumei Fu, Shizhong Zheng, Jianguo Lin, Jan Ryerse and Anping Chen
Molecular Pharmacology February 1, 2008, 73 (2) 399-409; DOI: https://doi.org/10.1124/mol.107.039818

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Research ArticleArticle

Curcumin Protects the Rat Liver from CCl4-Caused Injury and Fibrogenesis by Attenuating Oxidative Stress and Suppressing Inflammation

Yumei Fu, Shizhong Zheng, Jianguo Lin, Jan Ryerse and Anping Chen
Molecular Pharmacology February 1, 2008, 73 (2) 399-409; DOI: https://doi.org/10.1124/mol.107.039818
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