Effects of dietary beta-cyclodextrin in hypercholesterolaemic rats.
Beta-cyclodextrin is a compound that forms inclusion complexes with a variety of molecules, specially bile acids and sterols. This study examines the effects of beta-cyclodextrin on cholesterol and bile acid metabolism in hypercholesterolaemic rats. Male Wistar rats were divided into 4 groups that received during 7 weeks: control diet, 2% cholesterol diet (A), A+2.5% beta-cyclodextrin (B) and A+5% beta-cyclodextrin (C). The cholesterol-rich diet induced hepatomegaly and fatty liver and significantly reduced cholesterol, bile acid and phospholipid secretion. Addition of beta-cyclodextrin normalised biliary lipid secretion. Moreover, when compared to A, beta-cyclodextrin significantly lowered plasma phospholipid concentration (B: -21%; C: -29%) and the liver free/total cholesterol molar ratio (B: -40%; C: -38%), increased bile acid faecal output (B: +17%; C: +62%) and enhanced cholesterol 7alpha-hydroxylase activity (B:+50%; C : +100%)and mRNA levels (B: + 14%; C: +29%). 5% beta-cyclodextrin also reduced plasma triglycerides concentration (-38%). However, ALT and AST activities were significantly increased (B: +140% and +280%; C: +72% and +135%) and there was a high incidence of cell necrosis with portal inflammatory cell infiltration. Addition of beta-cyclodextrin to a cholesterol-rich diet results in a triglyceride-lowering action, enhancement of bile acid synthesis and excretion, and normalization of biliary lipid secretion, but produces a marked hepatotoxic effect.
Department of Physiology, University of León, 24071 León, Spain.
Victoria
V
García-Mediavilla
Carmen
C
Villares
Jesús M
JM
Culebras
Jose E
JE
Báyon
Javier
J
González-Gallego
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology* / Q000633:toxicity; D001219:Aspartate Aminotransferases / Q000097:blood; D001646:Bile / Q000378:metabolism; D001647:Bile Acids and Salts / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D002790:Cholesterol 7-alpha-Hydroxylase / Q000378:metabolism; D002791:Cholesterol, Dietary / Q000008:administration & dosage*; D003505:Cyclodextrins / Q000494:pharmacology* / Q000633:toxicity; D004032:Diet; D004435:Eating / Q000187:drug effects; D005243:Feces / Q000737:chemistry; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D015430:Weight Gain / Q000187:drug effects; D047392:beta-Cyclodextrins
D000924:Anticholesteremic Agents; D001647:Bile Acids and Salts; D002791:Cholesterol, Dietary; D003505:Cyclodextrins; D047392:beta-Cyclodextrins; D002784:Cholesterol; D002790:Cholesterol 7-alpha-Hydroxylase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; C031215:betadex