Distribution of tritiated dihydromicrocystin in swine

Richard R. Stotts, A. Robert Twardock, Wanda M. Haschek, Byoung W. Choi, Kenneth L. Rinehart, Val Richard Beasley

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Abstract

The distribution of tritiated dihydromicrocystin [ 3 H]2H-MCLR was studied in anesthetized specific-pathogen-free pigs. Two doses were administered i.m. and one dose was given via an isolated ileal loop. At 4 hr after i.v. administration of the toxin at 25 μg/kg, 64.6% of the total dose (%TD) was located in the liver, with smaller amounts distributed to the kidneys (1.2%TD), lungs (1.75%TD), heart (0.22%TD), ileum (0.13%TD) and spleen (0.04%TD). A similar distribution was found at 4 hr postdosing in pigs given 75 μg/kg, although the liver contained a lower fraction of the total dose, at 46.99%TD, and the kidneys had somewhat more, at 2.19%TD, than the low dose. At the high dose, the fractions of the amount given accounted for by the lungs (0.55%TD), heart (0.23%TD), ileum (0.20%TD) and spleen (0.07%TD) were similar to those at the low dose. The livers of the pigs given 75 μg/kg via the ileal loop, at 5 hr postdosing, contained 49.5%TD and the ileum had 33.94%TD. Smaller amounts were distributed to kidneys (1.04%TD), lungs (0.65%TD), heart (0.81%TD) and spleen (0.16%TD). The livers of both groups dosed at 75 μg/kg contained higher concentrations of toxin, but lower percentages of the total dose, than the livers of pigs dosed at 25 μg/kg. Larger increases in serum arginase in the two 75 μg/kg groups were associated with histological evidence of more severe liver damage than at the 25 μg/kg dose. Analysis of radiolabeled compounds from hepatic tissue using fast atom bombardment mass spectrometry determined that the primary constituent was [ 3 H]2H-MCLR, but two minor radioactive components were also isolated. These findings indicate that [ 3 H]2H-MCLR is rapidly concentrated in the liver of swine, whether given i.v. or via an isolated ileal loop, that at extremely toxic doses uptake is slowed, and that it is as toxicologically active as the parent compound.

Original languageEnglish (US)
Pages (from-to)937-953
Number of pages17
JournalToxicon
Volume35
Issue number6
DOIs
StatePublished - Jun 1 1997

All Science Journal Classification (ASJC) codes

  • Toxicology

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    Stotts, R. R., Twardock, A. R., Haschek, W. M., Choi, B. W., Rinehart, K. L., & Beasley, V. R. (1997). Distribution of tritiated dihydromicrocystin in swine. Toxicon, 35(6), 937-953. https://doi.org/10.1016/S0041-0101(96)00169-9