Retinyl palmitate reduces hepatic fibrosis in rats induced by dimethylnitrosamine or pig serum

Background/Aims: Lipid peroxidation has been found to be associated with It o cell activation. Ito cells are the principal collagen-producing cells and the main storage sites of retinoids. However, the relationship between ret inoids and hepatic fibrosis is complex. The aim of this study was to elucid ate the role of retinoids as a fibrosuppressant: the effects of retinoids o n hepatic fibrosis induced in rats by dimethylnitrosamine or pig serum, as well as on rat Ito cells in primary culture, were examined in order to asse ss the antioxidant activity of retinoids. Methods: Male Wistar rats were given a single injection of 40 mg/kg dimethy lnitrosamine or 0.5 mi PS twice weekly for 10 weeks. In each model, rats we re treated with retinyl palmitate for 2 weeks before hepatotoxin treatments or for the last 2 weeks of the treatments. The cumulative amount of retiny l palmitate administered in each experiment was 2, 10, or 20 x 10(4) IU/rat . Results: Retinyl palmitate treatment before or after administration of dime thylnitrosamine or pig serum suppressed the induction of hepatic fibrosis, restored hepatic retinyl palmitate levels, prevented increases in hepatic l evels of collagen and malondialdehyde, a product of lipid peroxidation, and prevented increases in deposition of type III collagen and the number of a lpha-smooth muscle actin (alpha-SMA) positive-Ito cells in the liver. Retin yl palmitate supplementation resulted in a dose-dependent reduction of a-SM A expression and an oxidative burst in cultured Ito cells. In addition, ret inyl palmitate inhibited Fe2+/adenosine 5'-diphosphate-induced lipid peroxi dation in rat liver mitochondria and showed radical scavenging activity. Conclusions: These findings suggest that retinyl palmitate may suppress the induction of hepatic fibrosis, at least in part, by the inhibition of Ito cell activation through its antioxidant activity.