Keywords

These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Interruption of Bile Acid Recirculation

Cholestyramine Binding

Purpose and Rationale

Cholesterol is metabolized in the liver by oxidation to bile acids which undergo enterohepatic circulation. In the untreated state, approximately 95 % of the bile acids that are secreted are reabsorbed and returned to the liver, while the small loss is replaced by de novo biosynthesis from cholesterol. Increased excretion of bile acids with the feces increases the rate of oxidation of cholesterol in the liver leading to a partial depletion of the hepatic cholesterol pool. A compensatory increase in uptake via the LDL receptors results in lower serum LDL levels. This can be achieved by addition of a bile acid-binding resin, e.g., cholestyramine, to the food. The binding of unconjugated and conjugated bile-salt anions can be tested in vitro (Johns and Bates 1969).

Procedure

Rabbits weighing 2.5–3 kg are switched from standard food to a diet containing 10–20 % polymeric basic-anion exchanging resin, e.g., cholestyramine. Cholesterol levels in serum are measured at the beginning and at the end of a 4-week feeding period.

Evaluation

Cholesterol levels as means ± SD are calculated for controls and treated animals and compared by statistical analysis.

Modification of the Method

Tennent et al. (1960) tested polymeric organic bases for action on blood cholesterol in 4-day experiments and in experiments of 7–8-week duration in cholesterol-fed White Leghorn cockerels. The birds were given a diet containing 2 % cholesterol and 5 % cotton-seed oil with or without addition of polymeric bases. The increase of cholesterol and the incidence of aortic atheromatosis were decreased by polymeric organic bases.

Day (1990) compared the hypocholesterolemic activities of the bile acid sequestrants cholestyramine and cholestipol hydrochloride in cholesterol-fed sea quail.

Quaternary ammonium conjugates of bile acid inhibited cholic acid binding and transport in everted ileal sacs of guinea pigs in vitro (Fears et al. 1990).

References and Further Reading

  • Ast M, Frishman WH (1990) Bile acid sequestrants. J Clin Pharmacol 30:99–106

  • Curtius HCh, Bürgi W (1966) Gaschromatographische Bestimmung des Serumcholesterins. Z klin Chem klin Biochem 4:38–42

  • Day ChE (1990) Comparison of hypocholesterolemic activities of the bile acid sequestrants cholestyramine and cholestipol hydrochloride in cholesterol fed sea quail. Artery 17:281–288

  • Fears R, Brown R, Ferres H, Grenier F, Tyrell AWR (1990) Effects of novel bile salts on cholesterol metabolism in rats and guinea-pigs. Biochem Pharmacol 40:2029–2037

  • Johns W, Bates T (1969) Quantification of the binding tendencies of cholestyramine I: effect of structure and added electrolytes on the binding of unconjugated and conjugated bile salt anions. J Pharm Sci 58:179–183

  • Kihara K, Toda H, Mori M, Hashimoto M, Mizogami S (1988) The bile acid binding and hypocholesterolemic activity of anion-exchange resins bearing the imidazolium salt group. Eur J Med Chem 23:411–415

  • Tennent DM, Siegel H, Zanetti ME, Kuron GW, Ott WH, Wolf FJ (1960) Plasma cholesterol lowering action of bile acid binding polymers in experimental animals. J Lipid Res 1:469–473

  • Toda H, Kihara K, Hashimoto M, Mizogami S (1988) Bile acid binding and hypocholesterolemic activity of a new anion exchange resin from 2-methylimidazol and epichlorhydrin. J Pharm Sci 77:531–533