Cholesterol kinetic analyses in copper-deficient rats

Ninety weanling male Sprague-Dawley rats were randomly allotted into two treatment groups (copper-deficient and adequate; less than 2 mg and 8 mg Cu/kg of diet. Feed and distilled water were provided ad libitum for 16 weeks. After 5 weeks of treatment, the rats were injected intraperitoneally with 6.35 microCI [4-14C]cholesterol/kg body weight. A disappearance curve of the serum cholesterol specific activity (SA) was obtained for each treatment group by killing one animal at 1, 2, 7, 14, 28, 42, 56, 70 and 77 days after the tracer injection. Disappearance curves of serum cholesterol SA were constructed for the rats fed the copper-adequate and copper-deficient diets. Each disappearance curve of cholesterol SA in the serum was subjected to a kinetic two-pool analysis. The size of the fast turning over cholesterol pool (pool A) and the half-life of pool A were significantly greater in rats fed the copper-deficient diet than the controls. In addition, copper deficiency decreased the rate of removal of cholesterol from pool A (KAA), decreased the irreversible removal of cholesterol from pool A (KA) and reduced the rate of transport of cholesterol (KAB) from pool A to the slowly exchangeable pool (pool B). However, copper deficiency did not alter the production rate of cholesterol (PRA) in pool A. Thus, the reduction in the rate of removal of cholesterol from pool A might have been responsible for the hypercholesterolemia observed previously in rats fed copper-deficient diets.