Acute effects of filipin on the plasmic, hepatic, and biliary cholesterol of the rat.
Twenty-one male Wistar rats, 13 weeks old, were fed ad libitum hyperlipidic diets (28% fats) loaded with cholesterol (1.2%) for 5 weeks. One group of 11 rats was fed saturated fats (diet group "S") and another group of 10 rats was fed polyunsaturated fats (diet group "PU"). On the day they were sacrificed 10 of the rats were injected intravenously with 1 mg of filipin. Contrary to the rats in diet group "PU," the rats in diet group "S" treated with filipin presented certain characteristics that were not found in the nontreated group: They provided evidence of biliary cholestasis accompanied by a decline in the level of secretion of bile salts and phospholipids into bile. The concentrations of both free and esterified cholesterol in plasma fell and the amount of (esterified) hepatic cholesterol rose, although there was no change due to the filipin in the amounts of hepatic phospholipids. Explanatory hypotheses for these phenomena were considered, first, at the site of plasma membranes where filipin binds selectively to the cholesterol in the membrane, causing a disruption which probably disturbs the absorbance of circulating lipoproteins, especially that of hepatocyte cells, particularly in diet group "PU." Second, the effects of filipin on subcellular membranes seem to disturb the secretion of lipids and lipoproteins into bile and plasma, especially in diet group "S." Last, at the intracellular level, filipin appears to have a blocking effect on the organelles involved in biliary lipid secretion. The activity of certain enzymes such as cholesterol esterase may also be blocked, particularly in diet group "S," which would explain the accumulation of esterified cholesterol in liver.
D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D001646:Bile / Q000187:drug effects* / Q000378:metabolism; D001647:Bile Acids and Salts / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects; D002784:Cholesterol / Q000097:blood / Q000378:metabolism*; D002788:Cholesterol Esters / Q000378:metabolism; D004041:Dietary Fats / Q000008:administration & dosage; D005224:Fats, Unsaturated / Q000008:administration & dosage; D005372:Filipin / Q000494:pharmacology*; D005966:Glucuronidase / Q000378:metabolism; D006949:Hyperlipidemias / Q000209:etiology / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008563:Membrane Lipids / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D011090:Polyenes / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism
D001647:Bile Acids and Salts; D002788:Cholesterol Esters; D004041:Dietary Fats; D005224:Fats, Unsaturated; D008563:Membrane Lipids; D010743:Phospholipids; D011090:Polyenes; D005372:Filipin; D002784:Cholesterol; D000410:Alanine Transaminase; D005966:Glucuronidase