Toxicokinetics of tritiated dihydromicrocystin-LR in swine

Richard R. Stotts, A. Robert Twardock, Gary D. Koritz, Wanda M. Haschek, Richard K. Manuel, William B. Hollis, Val R. Beasley

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Abstract

The toxicokinetics of tritiated dihydromicrocystin-LR ([3H]2H-MCLR) were studied in anesthetized, specific-pathogen-free pigs. Pigs were dosed with radiolabeled plus non-labeled 2H-MCLR at 25 or 75 μg/kg i.v., or via an isolated ileal loop at 75 μg/kg. The i.v. doses were rapidly removed from the blood. At either i.v. dose, more than half the radiolabel from [3H]2H-MCLR present in the blood at 1 min postdosing was cleared by 6 min. The blood clearance at the 75 μg/kg dose was slower than at the 25 μg/kg dose. Accordingly, at the high dose, the concentrations of the toxin in blood were disproportionately higher from 10 min after dosing until the study ended 4 hr later. The decreased clearance is presumably due to decreased elimination from the blood as a consequence of the hepatic injury that was observed histologically. Following administration of [3H]2H-MCLR at 75 μg/kg via the ileum, the maximal toxin concentration in blood was achieved at 90 min after dosing. At that time the [3H]2H-MCLR concentration in portal venous blood was 3.6 times higher than in peripheral venous blood. Although bile production varied, following i.v. dosing radioactivity was detected in bile as early as 12 min postdosing in one animal. This study demonstrated that [3H]2H-MCLR is rapidly removed from the blood of anesthetized swine and that excretion of the radiolabel into bile may begin within 30 min of dosing.

Original languageEnglish (US)
Pages (from-to)455-465
Number of pages11
JournalToxicon
Volume35
Issue number3
DOIs
Publication statusPublished - Mar 1 1997

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All Science Journal Classification (ASJC) codes

  • Toxicology

Cite this

Stotts, R. R., Twardock, A. R., Koritz, G. D., Haschek, W. M., Manuel, R. K., Hollis, W. B., & Beasley, V. R. (1997). Toxicokinetics of tritiated dihydromicrocystin-LR in swine. Toxicon, 35(3), 455-465. https://doi.org/10.1016/S0041-0101(96)00120-1