Effect of cholestyramine in normo-lipidemic swine

Abstract

The effects of cholestyramine on cholesterol balance parameters, bile acids and the enzyme activities of HMG-CoA reductase and cholesterol 7α-hydroxylase were studied in mash-fed young male Yorkshire swine. In addition, our previous results on cholestyramine effect in swine fed hyperlipidemic diet were compared with the results of the current study. Eight swine were divided into two groups: four were given 12 g cholestyramine daily for 2 weeks, and the other four served as the control. Serum cholesterol levels were monitored weekly. Feces were collected before and during the cholestyramine treatment for neutral and acidic steroid measurements and determination of other cholesterol balance parameters. Terminally, gallbladder bile was collected and bile acid composition and an in vitro cholestyramine adsorption study were carried out. Cholestyramine treatment in mash-fed swine resulted in the following significant changes: 1. (1) Whole body cholesterol synthesis increased to well above the mash level. 2. (2) Neutral steroid excretion was increased. 3. (3) The proportions of the more polar bile acid were increased in the bile and fecal bile acid excretion was increased with the increase accounted for by lithocholic acid. 4. (4) In vitro adsorption by cholestyramine of gallbladder bile acids from cholestyramine-treated swine was less than that of bile from untreated swine. This was considered to be the result of relative and/or absolute increases in the primary bile acids (more polar bile acids) in cholestyramine-treated swine. 5. (5) In vivo, cholestyramine removed very little bile acids as compared to that in vitro (31 vs 438 mg/g cholestyramine) suggesting the presence of competing factors in the intestine, e.g., fatty acids. 6. (6) Hepatic microsomal HMG-CoA reductase and cholesterol-7-α-hydroxylase activities reflected the fecal excretions of the steroids. However, ileal microsomal HMG-CoA reductase activities were not affected by cholestyramine treatment. On the basis of results from this study combined with those from previous studies, we conclude that: (1) the adsorption of bile acids on cholestyramine may be interfered with by the other dietary constituents such as fatty acids, and (2) cholestyramine treatment increases the relative ratio as well as absolute amount of primary bile acids and such bile acids may be adsorbed less effectively than other bile acids.