Dietary olive oil prevents carbon tetrachloride-induced hepatic fibrosis in mice.
OBJECTIVE
The specific purpose of this study was to investigate the effects of dietary olive oil on hepatic fibrosis induced by chronic administration of carbon tetrachloride (CCl(4)) in the mouse. In addition, the effects of oleic acid, a major component of olive oil, on activation of hepatic stellate cells (HSCs) were investigated in vitro.


METHODS
Mice were fed liquid diets containing either corn oil (control, AIN-93) or olive oil (6.25 g/L) throughout experiments. Animals were treated with CCl(4) for 4 weeks intraperitoneally. The mRNA expression of TGF-beta1 and collagen 1alpha2 (col1alpha2) in the liver was assessed by reverse transcriptase-polymerase chain reaction (RT-PCR). The HSCs were isolated from mice, and co-cultured with either oleic acid (100 microM) or linoleic acid (100 microM) for 2 days. The expression of alpha-smooth muscle actin (alpha-SMA) was assessed by immunohistochemistry. In addition, the production of hydroxyproline was determined.


RESULTS
Serum alanine aminotransferase levels and the mRNA expression of TGF-beta and collalpha2 were significantly reduced by treatment of olive oil. Dietary olive oil blunted the expression of alpha-SMA in the liverand liver injury and hepatic fibrosis were prevented by treatment of olive oil. The number of alpha-SMA positive cells was significantly lower in HSCs co-cultured with oleic acid than in those co-cultured with linoleic acid. Concentration of hydroxyproline in culture medium was significantly lower in cells co-cultured with oleic acid than in the control.


CONCLUSIONS
Dietary olive oil prevents CCl(4)-induced tissue injury and fibrosis in the liver. Since oleic acid inhibited activation of HSCs, oleic acid may play a key role on this mechanism.
Tanaka
Nobuyuki
N
First Department of Surgery, Faculty of Medicine, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi, 409-3898, Japan.
Kono
Hiroshi
H
Ishii
Kenichi
K
Hosomura
Naohiro
N
Fujii
Hideki
H
D000199:Actins / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity; D024042:Collagen Type I / Q000235:genetics; D003314:Corn Oil / Q000494:pharmacology; D004042:Dietary Fats, Unsaturated / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D055166:Hepatic Stellate Cells / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D019787:Linoleic Acid / Q000494:pharmacology; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019301:Oleic Acid / Q000302:isolation & purification / Q000494:pharmacology*; D000069463:Olive Oil; D010938:Plant Oils / Q000737:chemistry / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1 / Q000235:genetics
D000199:Actins; D024042:Collagen Type I; D004042:Dietary Fats, Unsaturated; D000069463:Olive Oil; D010938:Plant Oils; D053773:Transforming Growth Factor beta1; C544013:alpha-smooth muscle actin, mouse; D019301:Oleic Acid; D003314:Corn Oil; D019787:Linoleic Acid; D002251:Carbon Tetrachloride