Methyl palmitate prevents CCl4-induced liver fibrosis

Liver fibrosis is characterized by an excess of collagen fiber deposition, and it is known that Kupffer cells play an important role by immunomodulation of the toxic response. Methyl palmitate (MP) is an effective Kupffer cell inhibitor. The aim of this work was to evaluate the effect of MP on experimental liver fibrosis. Four groups were formed: the control group, which received the vehicles only; CCl4 group (0.4 g kg−1, i.p., three times a week, for eight weeks); CCl4 plus MP (300 mg kg−1, i.p., daily); and MP alone. Alanine aminotransferase was increased by CCl4, and MP did not prevent this increase. Lipid peroxidation was increased markedly by CCl4; again, MP was not able to prevent this effect. Fibrosis increased nearly 6‐fold (measured as liver hydroxyproline content) in the CCl4 group; MP preserved the normal content of collagen. These results were corroborated by histopathology. To elucidate the antifibrogenic mechanism of MP, we measured the production of TGF‐β; CCl4 increased this cytokine several‐fold, and MP abolished this increase. Collectively the present results indicate that MP possesses a strong antifibrogenic effect at least in the CCl4 model of fibrosis. The antifibrotic effect of MP is probably associated with its ability to reduce TGF‐β content, maybe by immunomodulation of Kupffer cells functioning. Copyright © 2008 John Wiley & Sons, Ltd.