Received for publication July 11, 2007.
Revised November 9, 2007.
Accepted for publication November 9, 2007.

Curcumin protects the rat liver from CCl₄-caused injury and fibrogenesis by attenuating oxidative stress and suppressing inflammation

Abstract

We previously demonstrated that curcumin, a polyphenolic antioxidant purified from turmeric, up regulated PPAR 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 IFN-, TNF- and IL-6. Furthermore, curcumin inhibits HSC activation by elevating the level of PPAR and reducing the abundance of PDGF, TGF-, 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 anti-fibrotic agent for the treatment of hepatic fibrosis.

Key words: PDGF, Growth hormone, PPARs, Regulation - transcriptional, Glutathione, Oxidative stress/antioxidants, Oxidative stress