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 peroxisome proliferator-activated receptor (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 (CCl 4 ) in rats and further explores the underlying mechanisms. We hypothesize that curcumin might protect the liver from CCl 4 -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-␥, tumor necrosis factor-␣, and interleukin-6. Furthermore, curcumin inhibits HSC activation by elevating the level of PPAR␥ and reducing the abundance of platelet-derived growth factor, transforming growth factor-␤, their receptors, and type I collagen. This study demonstrates that curcumin protects the rat liver from CCl 4 -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.

Helicobacter pylori promotes hepatic fibrosis in the animal model

“…Mice and rats were killed when known as inducing fibrotic stage by CCl 4 administration. [17][18][19] H. pylori infection for 4 months caused functional and morphological degenerative changes in hepatocytes, such as the depletion of glycogen particles, hydropic degeneration, binucleation and accumulation of numerous small fat droplets in our present research (Figures 7 and 8). These histological findings regarding hepatocytes suggest that H. pylori causes a disarrangement of hepatic architecture with some showing slight focal necrosis and inflammatory changes in spite of there being no severe hepatitis present in the liver samples used in this study (Figure 7).…”

“…CCl 4 was administered on three separate occasions over a 5-day period for 8 weeks to induce liver fibrosis. 17 From week 1, when constructing the animal model of hepatic injury was begun, the H. pylori strain ATCC 43504, 1.0 ml of inoculum per rat, was inoculated orally in a daily alternative manner with CCl 4 treatment. Rats were killed at the end of the eighth week; from each rat, blood samples were collected from the inferior vena cava, and the liver and stomach were removed.…”

Perilipin 5 restores the formation of lipid droplets in activated hepatic stellate cells and inhibits their activation

“…Antibodies used in this study were previously discussed, [21][22][23] and purchased from Santa Cruz Biotechnology (Santa Cruz, CA, USA), except specific indications.…”

“…The experiments were conducted as we previously described, 21 using goat polyclonal primary antibody against Plin5 (1:50, sc-240627, Santa Cruz, CA, USA) and donkey anti-goat IgG secondary antibody conjugated with fluorescent Texas Red dye (1:300, cat#705-075-147, Jackson ImmunoResearch, PA, USA). Nuclei were stained by a mounting solution with DAPI.…”

“…21 Freshly isolated HSC were used for RNA preparation, or were cultured in Dulbecco's modified Eagle's medium supplemented with 20% of fetal bovine serum. Cells were passaged in Dulbecco's modified Eagle's medium with 10% of fetal bovine serum.…”