Lymphatic and portal vein absorption of organochlorine compounds in rats

Abstract

The route of absorption of ingested compounds is a determinant of their distribution and metabolism. Portal vein absorption results in direct transport to the liver, where metabolism may take place before extrahepatic delivery. Lymphatic absorption can result in delivery of parent compound to nonhepatic tissues. Understanding the fate of an ingested compound requires determination of the importance of each of these routes. Portal vein absorption can be estimated from the difference in concentrations of an ingested compound between the portal vein and peripheral vessel blood. To make these estimations, one must make assumptions on the basis of estimates of flow rate and dilution. We report here methodology that allows a direct measurement of portal vein absorption that is independent of these assumptions. Mesenteric lymph was diverted from rats by cannulation. Portal blood was sampled after duodenal infusion of a bolus of compound of interest along with a portal absorption marker, 3-O-methylglucose. Since lymph was diverted, the appearance in portal blood was solely the result of portal absorption. Absorption was quantified by the areas under the curve for the compound and marker. Portal absorption was a function of the octanol/water partition coefficients for four organochlorine compounds: hexachlorobenzene, pentachlorophenol, DDT, and its metabolite 1,1,1-trichloro-2,2-bischlorophenylethylene.

Fig. 1.

[¹⁴C]hexachlorobenzene (HCB) and [³H]3-O-methylglucose (OMG) in portal vein plasma. Rats fitted with both mesenteric lymph and portal vein cannulas were gavaged with a bolus of the isotope-labeled compounds. Periodic samples of 100 μl of blood were analyzed (n = 4; means ± SE shown).

Fig. 2.

The appearance of [¹⁴C]HCB and [³H]OMG in red blood cells (RBCs). RBCs from the portal vein blood from the study described in Fig. 1 were analyzed.

Fig. 3.

The appearance of [¹⁴C]DDT and [³H]triolein in portal blood plasma after duodenal infusion. The study was carried out as described in Fig. 1 (n = 4; means ± SE shown), except that [³H]triolein, which is normally entirely absorbed lymphatically, was used as a marker instead of [³H]OMG.

Fig. 4.

The appearance of [¹⁴C]DDT and [³H]OMG in portal vein plasma after intraduodenal administration. The study was carried out as described in Fig. 1 (n = 4; means ± SE shown).

Fig. 5.

The relative distribution of [¹⁴C]DDT among plasma lipoproteins sampled from the portal vein at times after gavage. Plasma from the animals in the study described in Fig. 4 was pooled, separated by ultracentrifugation with solutions of KBr, and assayed for radioactivity.

Fig. 6.

The appearance of [¹⁴C]pentachlorophenol (PCP) and [³H]OMG in portal vein plasma. The study was carried out as described in Fig. 1 (n = 7; means ± SE shown).

Fig. 7.

The relative distribution of [¹⁴C]PCP among plasma lipoproteins sampled from the portal vein at times after gavage. Plasma from the animals in the study described in Fig. 5 was pooled, separated by ultracentrifugation with solutions of KBr, and assayed for radioactivity.

Fig. 8.

The appearance of [¹⁴C]1,1,1-trichloro-2,2-bischlorophenylethylene (DDE) and [³H]OMG in portal vein plasma. The study was carried out as described in Fig. 1 (n = 6; means ± SE shown).

Fig. 9.

The relative distribution of [¹⁴C]PCP among plasma lipoproteins sampled from the portal vein at times after gavage. Plasma from the animals in the study described in Fig. 5 was pooled, separated by ultracentrifugation with solutions of KBr, and assayed for radioactivity.

Fig. 10.

Distribution of lipophiles within the enterocyte. Triacylglycerols are resynthesized from fat digestion products to form prechylomicrons (PreCM). Lipophiles such as HCB can partition into lipid-rich prechylomicrons, chylomicrons (CM), and fatty acid binding proteins (FABP) during movement from the enterocyte into lymph or portal blood. SER, smooth endoplasmic reticulum.