EFFECT OF THE PLANT-COMPOUND INDOLE-3-CARBINOL ON HEPATIC CHOLESTEROLHOMEOSTASIS

The aim of this study was to elucidate the effects of the compound ind ole-3-carbinol (I3C), which is found in cruciferous vegetables, on hep atic cholesterol homoeostasis and metabolism in male CD-1 mice. Oral a dministration of 500 and 750 mg I3C/kg/day to mice for 1 wk resulted i n increased liver mass and microsomal protein content. Hepatic microso mal cholesterol levels were not significantly altered following treatm ent with 100 and 250 mg I3C/kg/day, but were significantly decreased f ollowing treatment with 500 and 750 mg/kg/day. Conversely, the lower d oses of I3C administered decreased serum cholesterol levels whereas th e higher doses of I3C had no effect on this parameter. Alterations in cholesterol homoeostasis by I3C were not related to liver hypertrophy, since administration of phenobarbital to mice increased liver size, b ut had no significant effect on hepatic microsomal or serum cholestero l levels. Activities of the hepatic enzymes cholesterol ester hydrolas e and cholesterol 7 alpha-hydroxylase were not altered by I3C. However , 500 and 750 mg I3C/kg/day elevated the activity of hepatic acyl-CoA: cholesterol acyltransferase (ACAT), the enzyme responsible for the for mation of hepatic cholesteryl esters. These results demonstrate that ( a) I3C lowers serum cholesterol levels at concentrations that have no discernible effect on hepatic cholesterol homoeostasis, and (b) at hig her doses of I3C, hepatic microsomal cholesterol levels are significan tly lowered and ACAT activity is significantly elevated. These latter effects are not accompanied by changes in serum cholesterol levels and may represent compensatory mechanisms to restore cholesterol homoeost asis in the body. Mechanisms responsible for the effects of I3C on cho lesterol homoeostasis are proposed.