Distribution of tritiated dihydromicrocystin in swine.
The distribution of tritiated dihydromicrocystin [3H]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 micrograms/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 micrograms/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 micrograms/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 micrograms/kg contained higher concentrations of toxin, but lower percentages of the total dose, than the livers of pigs dosed at 25 micrograms/kg. Larger increases in serum arginase in the two 75 micrograms/kg groups were associated with histological evidence of more severe liver damage than at the 25 micrograms/kg dose. Analysis of radiolabeled 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.
Stotts
R R
RR
Department of Veterinary Biosciences, University of Illinois, Urbana, USA.
Twardock
A R
AR
Haschek
W M
WM
Choi
B W
BW
Rinehart
K L
KL
Beasley
V R
VR
D000818:Animals; D001119:Arginase / Q000097:blood; D001646:Bile / Q000378:metabolism; D000458:Cyanobacteria; D005260:Female; D008099:Liver / Q000378:metabolism; D008387:Marine Toxins / Q000493:pharmacokinetics* / Q000652:urine; D010456:Peptides, Cyclic / Q000493:pharmacokinetics* / Q000652:urine; D013552:Swine; D014018:Tissue Distribution; D014316:Tritium
D008387:Marine Toxins; D010456:Peptides, Cyclic; D014316:Tritium; C064961:dihydromicrocystin LR; D001119:Arginase