Methyl palmitate prevents CCl(4)-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; CCl(4) group (0.4 g kg(-1), i.p., three times a week, for eight weeks); CCl(4) plus MP (300 mg kg(-1), i.p., daily); and MP alone. Alanine aminotransferase was increased by CCl(4), and MP did not prevent this increase. Lipid peroxidation was increased markedly by CCl(4); again, MP was not able to prevent this effect. Fibrosis increased nearly 6-fold (measured as liver hydroxyproline content) in the CCl(4) 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-beta; CCl(4) 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 CCl(4) model of fibrosis. The antifibrotic effect of MP is probably associated with its ability to reduce TGF-beta content, maybe by immunomodulation of Kupffer cells functioning.
Rodríguez-Rivera
Adriana
A
Sección Externa de Farmacología, Cinvestav-IPN, México, D.F., México.
Galicia-Moreno
Marina
M
Reyes-Gordillo
Karina
K
Segovia
José
J
Vergara
Paula
P
Moreno
Mario G
MG
Shibayama
Mineko
M
Tsutsumi
Víctor
V
Muriel
Pablo
P
D000818:Animals; D001711:Biotransformation / Q000187:drug effects; D015153:Blotting, Western; D002251:Carbon Tetrachloride / Q000378:metabolism / Q000633:toxicity; D002252:Carbon Tetrachloride Poisoning / Q000473:pathology / Q000517:prevention & control*; D003094:Collagen / Q000032:analysis / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D006651:Histocytochemistry; D015227:Lipid Peroxidation / Q000187:drug effects; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D009336:Necrosis; D010168:Palmitates / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D016212:Transforming Growth Factor beta / Q000378:metabolism
D010168:Palmitates; D016212:Transforming Growth Factor beta; D003094:Collagen; D002251:Carbon Tetrachloride; C019012:methyl palmitate