Effects of dietary beta-cyclodextrin in hypercholesterolaemic rats

Abstract

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.