COMPARISON OF OLESTRA ABSORPTION IN GUINEA-PIGS WITH NORMAL AND COMPROMISED GASTROINTESTINAL TRACTS

(F)emale guinea pigs (12/group) were given a single dose of [C-14]oles tra by gavage after consuming either 3% poligeenan in tap water (Compr omised group) or just tap water (Normal group) for 5 weeks. A Sentinel group (N = 2) was given 3% poligeenan for 5 weeks. Ten sentinel anima ls were killed 1 day before and 10 1 day after the other animals were dosed with [C-14]olestra and their gastrointestinal tracts were examin ed by histology. The Compromised and Normal animals were endoscoped ju st before dosing with [C-14]olestra. Urine and feces were collected co ntinuously and CO2 was collected for 7 days after dosing. The samples were analyzed for C-14 and urine was also analyzed for [C-14]sucrose. Animals (3/group) were killed 1, 3, 7, and 21 days after dosing, and t issues were collected and assayed for C-14. Tissue lipids were extract ed, fractionated by high-pressure liquid chromatography, and analyzed for [C-14]olestra by liquid scintillation. Animals fed poligeenan show ed mucosal edema, congestion, ulceration, and fibrin deposition within the distal colon and rectum. Histology revealed inflammation, epithel ial degeneration, and multifocal ulceration of the cecum, distal colon , and rectum. The gastrointestinal mucosae of nonpoligeenan fed animal s were normal. No [C-14]olestra was detected in liver lipids and no [C -14]sucrose was found in the urine for any animal in the Normal or Com promised groups, indicating that intact olestra was not absorbed. The amount, distribution, and elimination of absorbed C-14 did not differ between guinea pigs with normal and compromised gastrointestinal tract s. The poligeenan-treated animals displayed mucosal damage similar to that seen in human inflammatory bowel diseases; therefore, these resul ts suggest that patients with inflammatory bowel conditions will not a bsorb olestra to any greater extent than normal healthy people. (C) 19 97 Society of Toxicology.