Effect of the plant compound indole-3-carbinol on hepatic cholesterol homoeostasis.
The aim of this study was to elucidate the effects of the compound indole-3-carbinol (I3C), which is found in cruciferous vegetables, on hepatic cholesterol homoeostasis and metabolism in male CD-1 mice. Oral administration of 500 and 750 mg I3C/kg/day to mice for 1 wk resulted in increased liver mass and microsomal protein content. Hepatic microsomal cholesterol levels were not significantly altered following treatment with 100 and 250 mg I3C/kg/day, but were significantly decreased following treatment with 500 and 750 mg/kg/day. Conversely, the lower doses of I3C administered decreased serum cholesterol levels whereas the 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, but had no significant effect on hepatic microsomal or serum cholesterol levels. Activities of the hepatic enzymes cholesterol ester hydrolase 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 formation 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 higher doses of I3C, hepatic microsomal cholesterol levels are significantly 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 homoeostasis in the body. Mechanisms responsible for the effects of I3C on cholesterol homoeostasis are proposed.
LeBlanc
G A
GA
Department of Toxicology, North Carolina State University, Raleigh 27695.
Stuart
J D
JD
Dunn
S E
SE
Baldwin
W S
WS
D000818:Animals; D002784:Cholesterol / Q000097:blood / Q000737:chemistry*; D002790:Cholesterol 7-alpha-Hydroxylase / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects; D007211:Indoles / Q000494:pharmacology*; D008099:Liver / Q000737:chemistry / Q000187:drug effects*; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000737:chemistry / Q000187:drug effects; D002787:Sterol Esterase / Q000378:metabolism; D002785:Sterol O-Acyltransferase / Q000378:metabolism
D007211:Indoles; D002784:Cholesterol; C016517:indole-3-carbinol; D002790:Cholesterol 7-alpha-Hydroxylase; D002785:Sterol O-Acyltransferase; D002787:Sterol Esterase