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]olestra by gavage after consuming either 3% poligeenan in tap water (Compromised group) or just tap water (Normal group) for 5 weeks. A Sentinel group (N = 2) was given 3% poligeenan for 5 weeks. Ten sentinel animals were killed 1 day before and 10 1 day after the other animals were dosed with [C-14]olestra and their gastrointestinal tracts were examined by histology. The Compromised and Normal animals were endoscoped just before dosing with [C-14]olestra. Urine and feces were collected continuously 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 tissues were collected and assayed for C-14. Tissue lipids were extracted, fractionated by high-pressure liquid chromatography, and analyzed for [C-14]olestra by liquid scintillation. Animals fed poligeenan showed mucosal edema, congestion, ulceration, and fibrin deposition within the distal colon and rectum. Histology revealed inflammation, epithelial degeneration, and multifocal ulceration of the cecum, distal colon, and rectum. The gastrointestinal mucosae of nonpoligeenan fed animals 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 Compromised 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 tracts. The poligeenan-treated animals displayed mucosal damage similar to that seen in human inflammatory bowel diseases; therefore, these results suggest that patients with inflammatory bowel conditions will not absorb olestra to any greater extent than normal healthy people. (C) 1997 Society of Toxicology.