Comparison of olestra absorption in guinea pigs with normal and compromised gastrointestinal tracts.

G. Daher, K. Lawson, P. H. Long, D. Tallmadge, A. Boothe, P. Vanderploeg, K. W. Miller
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引用次数: 2

Abstract

Female guinea pigs (12/group) were given a single dose of [14C]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 [14C]olestra and their gastrointestinal tracts were examined by histology. The Compromised and Normal animals were endoscoped just before dosing with [14C]olestra. Urine and feces were collected continuously and CO2 was collected for 7 days after dosing. The samples were analyzed for 14C and urine was also analyzed for [14C]sucrose. Animals (3/group) were killed 1, 3, 7, and 21 days after dosing, and tissues were collected and assayed for 14C. Tissue lipids were extracted, fractionated by high-pressure liquid chromatography, and analyzed for [14C]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 [14C]olestra was detected in liver lipids and no [14C]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 14C 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.
豚鼠正常和受损胃肠道对奥利斯特拉吸收的比较。
雌性豚鼠(12只/组)在饮用3%的自来水(受损组)或仅饮用自来水(正常组)5周后,通过灌胃给予单剂量[14C]奥利斯特拉。哨点组(N = 2)给予3%聚乙二醇,疗程5周。在给药前1天处死10只哨兵动物,在给药后1天处死10只哨兵动物,并对其胃肠道进行组织学检查。在给药前,对受损动物和正常动物进行内窥镜检查。连续收集尿液和粪便,并在给药后7天收集二氧化碳。对样品进行了14C分析,对尿液也进行了[14C]蔗糖分析。给药后1、3、7、21 d处死动物(3只/组),收集组织检测14C含量。组织脂质提取,高压液相色谱分离,液体闪烁分析[14C]olestra。饲喂聚乙二醇的动物出现粘膜水肿、充血、溃疡和远端结肠和直肠内纤维蛋白沉积。组织学显示炎症,上皮变性,盲肠,远端结肠和直肠多灶性溃疡。非聚乙烯喂养动物胃肠道粘膜正常。正常组和受损组动物的肝脏脂质中未检测到[14C]olestra,尿液中未发现[14C]蔗糖,表明未吸收完整的olestra。吸收14C的量、分布和消除在胃肠道正常和受损的豚鼠之间没有差异。经聚乙二醇处理的动物表现出与人类炎症性肠病相似的粘膜损伤;因此,这些结果表明,炎症性肠病患者不会比正常健康人吸收更多的奥利斯特拉。
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