Cholesterol-lowering and gallstone-preventing action of chitosans with different degrees of deacetylation in hamsters fed cholesterol-rich diets

Abstract

The lipid-lowering potential of chitin and chitosan (CHI) and their protective effect against cholesterol gallstone formation was investigated by feeding male Golden Syrian hamsters gallstone-inducing diets. Since the physicochemical properties like degree of deacetylation or viscosity are thought to be involved in the hypocholesterolemic action of CHI, two varieties of CHI, a 92% and a 79% deacetylated CHI (CHI92 and CHI79) were tested. Hamsters were fed semipurified, gallstone-inducing diets containing 5% fat, 0.4% cholesterol and 10% cellulose with or without supplements of chitin (8%) or the two CHIs (8% and 4%). After 5 weeks, 8% CHI79 significantly reduced plasma lipids (total cholesterol (TC): 4.5±0.7 vs 10.1±3.9 mmol/L and triglycerides (TG): 2.9±1.5 vs 7.3±3.6 mmol/L compared to the control diet), whereas 8% CHI92 produced only a minor hypocholesterolemic effect (−10%). Feeding 8% CHI92 or CHI79 caused a significant reduction in food intake, body weight gain and liver weight. The adverse effect on food intake and growth was lessened by feeding 4% CHI92 or CHI79, but the differences were still significant for CHI92. The supplementation with 4% of both CHIs resulted in a significant lowering of plasma cholesterol with a reduction in TC of 38% with CHI92 and 32% with CHI79 compared to the control diet. Hepatic cholesterol was significantly decreased with 8% CHI79, whereas 8% CHI92 caused only a negligible reduction. The 4% supplement of CHI92 did not alter cholesterol accumulation in the liver, but hepatic total cholesterol was significantly increased with 4% CHI79. While the 8% supplements of both CHIs completely inhibited cholesterol gallstone formation, 4% CHI92 or CHI79 added to the diet had no preventive effect and a 90% incidence of cholesterol gallstones was observed. 8% chitin produced no apparent effects on plasma, hepatic and biliary lipids. Whereas 8% CHI79 significantly increased the cholate : chenodeoxycholate ratio of gallbladder bile by decreasing particularly taurochenodeoxycholate, 8% CHI92 had no distinct impact on bile acid composition. The 4% supplements of CHI92 or CHI79 did not alter biliary lipids and bile acid distribution. The dried fecal weight was doubled by feeding 8% and 4% of CHI92 or CHI79 compared to the control diet. Whereas the daily excretion of neutral sterols was significantly expanded with the 8% supplements of CHI92 and CHI 79, only CHI79 caused also a 1.9-fold increase in the daily bile acid excretion. The supplementation with 4% of CHI92 or CHI79 did not significantly change fecal excretion of bile acids or neutral sterols although daily excretion of neutral sterols was increased by 20%. These data demonstrate that in hamsters feeding CHI is associated with a reduced food intake and that the cholesterol-lowering effect seems mainly related to an increase in the fecal excretion of neutral sterols.