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Distribution of tritiated dihydromicrocystin in swine

Identifieur interne : 001685 ( Istex/Corpus ); précédent : 001684; suivant : 001686

Distribution of tritiated dihydromicrocystin in swine

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

Source :

RBID : ISTEX:B3CC0187208543A58510F1BB708B5ECF516510AF

Abstract

The distribution of tritiated dihydromicrocystin i [3H]2H-MCLR was studied in anesthetized specific-pathogen-free pig. 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 small 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 dose 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 radiolabelled compounds from hepatic tissue using fast atom bombardment mass spectrometry determined that the primary constituent was [3H]2H-MCLR, but two minor radioactive components were also isolated. These findings indicate that [3H]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.

Url:
DOI: 10.1016/S0041-0101(96)00169-9

Links to Exploration step

ISTEX:B3CC0187208543A58510F1BB708B5ECF516510AF

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<ce:textfn>Department of Veterinary Pathobiology, University of Illinois, Urbana, IL 610801, U.S.A.</ce:textfn>
</ce:affiliation>
<ce:affiliation id="AFF3">
<ce:label>3</ce:label>
<ce:textfn>Department of Chemistry, University of Illinois, Urbana, IL 610801, U.S.A.</ce:textfn>
</ce:affiliation>
<ce:correspondence id="COR1">
<ce:label></ce:label>
<ce:text>Author to whom correspondence should be addressed.</ce:text>
</ce:correspondence>
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<ce:date-received day="21" month="3" year="1996"></ce:date-received>
<ce:date-accepted day="16" month="8" year="1996"></ce:date-accepted>
<ce:abstract>
<ce:section-title>Abstract</ce:section-title>
<ce:abstract-sec>
<ce:simple-para>The distribution of tritiated dihydromicrocystin i [
<ce:sup loc="pre">3</ce:sup>
H]2H-MCLR was studied in anesthetized specific-pathogen-free pig. 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 small 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 dose 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 radiolabelled compounds from hepatic tissue using fast atom bombardment mass spectrometry determined that the primary constituent was [
<ce:sup loc="pre">3</ce:sup>
H]2H-MCLR, but two minor radioactive components were also isolated. These findings indicate that [
<ce:sup loc="pre">3</ce:sup>
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.</ce:simple-para>
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<title>Distribution of tritiated dihydromicrocystin in swine</title>
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<title>Distribution of tritiated dihydromicrocystin in swine</title>
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<name type="personal">
<namePart type="given">Richard R.</namePart>
<namePart type="family">Stotts</namePart>
<affiliation>Department of Veterinary Biosciences, University of Illinois, Urbana, IL 610801, U.S.A.</affiliation>
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<name type="personal">
<namePart type="given">A.Robert</namePart>
<namePart type="family">Twardock</namePart>
<affiliation>Department of Veterinary Biosciences, University of Illinois, Urbana, IL 610801, U.S.A.</affiliation>
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<name type="personal">
<namePart type="given">Wanda M.</namePart>
<namePart type="family">Haschek</namePart>
<affiliation>Department of Veterinary Pathobiology, University of Illinois, Urbana, IL 610801, U.S.A.</affiliation>
<role>
<roleTerm type="text">author</roleTerm>
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</name>
<name type="personal">
<namePart type="given">Byoung W.</namePart>
<namePart type="family">Choi</namePart>
<affiliation>Department of Chemistry, University of Illinois, Urbana, IL 610801, U.S.A.</affiliation>
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</name>
<name type="personal">
<namePart type="given">Kenneth L.</namePart>
<namePart type="family">Rinehart</namePart>
<affiliation>Department of Chemistry, University of Illinois, Urbana, IL 610801, U.S.A.</affiliation>
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</name>
<name type="personal">
<namePart type="given">Val R.</namePart>
<namePart type="family">Beasley</namePart>
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<affiliation>Department of Veterinary Biosciences, University of Illinois, Urbana, IL 610801, U.S.A.</affiliation>
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<abstract lang="en">The distribution of tritiated dihydromicrocystin i [3H]2H-MCLR was studied in anesthetized specific-pathogen-free pig. 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 small 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 dose 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 radiolabelled compounds from hepatic tissue using fast atom bombardment mass spectrometry determined that the primary constituent was [3H]2H-MCLR, but two minor radioactive components were also isolated. These findings indicate that [3H]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.</abstract>
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