The metabolism of the xenobiotic triacylglycerols, rac-1- and sn-2- (3-phenoxybenzoyl)-dipalmitoylglycerol, following intravenous administration to the rat |
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Authors: | JN Haselden PF Dodds DH Hutson |
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Affiliation: | Department of Biological Sciences, Wye College, University of London, Ashford, Kent, UK. |
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Abstract: | The metabolism of 3-phenoxybenzoic acid (3PBA) in the form of triacylglycerol conjugates was compared with that of non-esterified 3PBA. Three radiolabeled triacylglycerols (rac-1-(3-phenoxy-[ring-14C]-benzoyl)-2,3-dipalmitoylglycerol (1(3PBA)DPG), sn-2-(3-phenoxy-[ring-14C]benzoyl)-1,3-dipalmitoylglycerol (2(3PBA)DPG) and the "natural" tri-[1-14C]oleoylglycerol) were incorporated into rat VLDL. Nonesterified 3PBA was prepared in rat serum albumin solution. Each preparation was administered i.v. to rats and serial blood samples were taken during the subsequent 6 hr. Urine and faeces were collected and tissue residues determined at 6 hr and 48 hr after administration. Biphasic elimination of 3PBA was observed with half-lives of 18 min and 2 hr. The triacylglycerols showed a rapid first phase and a longer second phase half-life: trioleoylglycerol 26 hr, 1(3PBA)DPG 7.6 hr and 2(3PBA)DPG 17.3 hr. The majority (63-76%) of 3PBA (whether esterified or not) was eliminated within 24 hr in urine, which contained similar profiles of metabolites. The triacylglycerols gave rise to higher tissue residues than did non-esterified 3PBA, particularly in adipose tissue which alone was not significantly depleted of radioactivity between 6 and 48 hr. The results accord with the rapid association of the VLDL-(3PBA)DPG complexes with lipoprotein lipase of the capillary epithelium, followed by hydrolysis to 3PBA, metabolism and elimination but with a proportion being redistributed into adipose tissue, re-esterified and then eliminated relatively slowly. |
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