Intestinal absorption: studies of absorption of certain natural lipids and lipophilic xenobiotics

Hall, Jennifer Lynn (1987) Intestinal absorption: studies of absorption of certain natural lipids and lipophilic xenobiotics. Masters thesis, Memorial University of Newfoundland.

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Abstract

The uptake of nutrient lipids by the absorptive cell of the small intestinal mucbsa is influenced by a number of factors. Some lipophilic xenobiotic compounds are also absorbed by the enterocyte in conjunction with the nutrient lipid. The interaction that occurs between these compounds and nutrient lipids is of toxicological and physiological interest. The chylomicron appearance time (the interval between introduction of ¹⁴C-oleic acid and the first appearance of ¹⁴C-labeled chylomicrons in thoracic duct lymph) is an effective tool in monitoring changes in the handling of the first lipid molecules being processed by the enterocyte. The chylomicron appearance time in control animals is highly reproducible and agrees well with previously published work. -- Polycyclic aromatic hydrocarbons such as 7,12-dimethylbenz[a|anthracene (DMBA) are known carcinogens and are readily absorbed from the gastrointestinal tract. Due to their lipophilic nature, a substantial proportion of the absorbed xenobiotic can be transported in lymph chylomicrons. Of the PAHs tested, only DMBA was found to exert any effect on the chylomicron appearance time resulting in an appearance time of 23.08 ± 2.10 minutes as compared to a control value of 10.81 ± 1.03 minutes (p < 0.001). These results indicate that the inclusion of DMBA in a nutrient lipid test meal significantly retards the normal process of uptake and/or processing of nutrient lipids within the enterocyte. -- Exposure to 10μmol DMBA several hours prior to test meal administration, still resulted a delay in chylomicron appearance time. Triglyceride flux analysis for three hours following test meal administration indicates a transient effect of DMBA since the total triglyceride outputs in both control and DMBA-treated rats were not significantly different. -- Subsequent studies used the chylomicron appearance time technique to determine the effects of other lipophilic compounds on lipid absorption Cholesterol had no effect on the chylomicron appearance time but the hydrophobic surfactant Pluronic L-81 delayed the the appearance of the radiolabel [16.60 ± 0.77 minutes, p < 0.01]. This result supports the report attributing hypolipidemic activity to this compound. -- The efficiency of the α-glycerophosphate pathway compared with the monoglyceride pathway for triglyceride resynthesis was examined using the chylomicron appearance time technique. Three groups of rats were used for this study. Group A received a lipid emulsion test meal containing 1-monoolein as its source of monoglyceride. Group B received a test meal containing 2-monoolein and Group C received a test meal without any monoglyceride present. The chylomicron appearance times for these three groups did not differ significantly. This indicates that the α-glycerophosphate pathway is capable of handling the first few molecules of lipid as efficiently as the monoglyceride pathway despite the higher energy cost required to do so.

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