EFFECTS OF DIETARY-FAT LEVELS ON THE ABSORPTION AND TISSUE ACCUMULATION OF PROBUCOL IN THE RAT

The effects of dietary fat level on the absorption and tissue accumula tion of probucol (PB, CAS 23288-49-5) were studied in male Wistar rats . Addition of 1% PB (w/w) to the diets as compared to the diets withou t an addition (P) resulted in a decrease in the concentration of both serum and high-density lipoprotein (HDL) cholesterol as well as TBA-re active substances (TBARS), without influencing food intake or growth. When rats were fed with the PB diet, the apparent intestinal absorptio n of PB ws 7.9%, while the serum PB level was 5 mu g/ml. The tissue di stribution of PB, when expressed per g of tissue, was highest in the a drenal glands, followed by the liver, heart, epididymal adipose tissue s, kidneys, lung spleen, and testes. The addition of 10% olive oil (PB O) to the PB diet (w/w) appeared to double the PB diet-induced increas e in apparent intestinal absorption and the serum concentration of PB. Furthermore, compared with the PB diet, the PBO diet caused 3- to 4-f old higher accumulation of PB in the liver and its subcellular fractio ns and 2-fold higher accumulation in the spleen. However, ther was no further accumulation of the drug in the heart, kidneys, lungs, and tes tes. Incorporation of the drugs into adipose tissues was significantly lower with the PBO diet than with the PB diet. These results suggest that dietary manipulation leads to changes in the intestinal absorptio n and serum level of PB.