Reevaluation and application of the dual-isotope plasma ratio method for the measurement of intestinal cholesterol absorption in the hamster.

These experiments systematically evaluated the dual-isotope plasma ratio method for measuring intestinal cholesterol absorption in the hamster. It was found that while the ratio of the 3H- and 14C-labeled cholesterol in the plasma, relative to the respective dose of each that was given, became constant by 72 h after their administration, the percent cholesterol absorption was lower in animals that were fasted before dosing (35.7 +/- 5.5%) than in their fed controls (47.5 +/- 3.7%). Furthermore, the percent absorption found 72 h after dosing varied greatly, depending on whether the intragastric dose of labeled cholesterol was administered in medium chain triglyceride (MCT) oil (46.2 +/- 2.3%), olive oil (63.9 +/- 11.2%), or safflower oil (74.6 +/- 4.5%). The level of absorption was not different between hamsters that had unrestricted (46.3 +/- 1.6%) and restricted (43.8 +/- 2.2%) access to their stools during the 72 h after dosing. Other experiments, using only hamsters in the fed state and MCT oil as the intragastric dosing medium, showed that the percent cholesterol absorption could be made to vary over a wide range using treatments known to produce such effects in humans. Thus, feeding either surfomer, cholestyramine, ursodeoxycholic acid, or CI-976, a new inhibitor of acyl-CoA:cholesterol acyltransferase, significantly blocked cholesterol absorption, whereas the addition of either cholic acid or increasing amounts of oil to the diet had the opposite effect. The modified dual-isotope plasma ratio method described here provides a simpler and more physiologic approach to the routine measurement of cholesterol absorption in the hamster and similar small animal models.