DISTRIBUTION OF TRITIATED DIHYDROMICROCYSTIN IN SWINE

The distribution of tritiated dihydromicrocystin [H-3]2H-MCLR was stud ied in anesthetized specific-pathogen-free pigs. Two doses were admini stered i.m. and one dose was given via an isolated ileal loop. At 4 hr after i.v. administration of the toxin at 25 mu g/kg, 64.6% of the to tal dose (%TD) was located in the liver, with smaller amounts distribu ted 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 h r postdosing in pigs given 75 mu g/kg, although the liver contained a lower fraction of the total dose, at 46.99%TD, and the kidneys had som ewhat more, at 2.19%TD, than the low dose. At the high dose, the fract ions 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 a t the low dose. The livers of the pigs given 75 mu g/kg via the ileal loop, at 5 hr postdosing, contained 49.5% TD and the ileum had 33.94%T D. 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 d osed at 75 mu g/kg contained higher concentrations of toxin, but lower percentages of the total dose, than the livers of pigs dosed at 25 mu g/kg. Larger increases in serum arginase in the two 75 mu g/kg groups were associated with histological evidence of more severe liver damag e than at the 25 mu g/kg dose. Analysis of radiolabeled compounds from hepatic tissue using fast atom bombardment mass spectrometry determin ed that the primary constituent was [H-3]2H-MCLR, but two minor radioa ctive components were also isolated. These findings indicate that [H-3 ]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 upta ke is slowed, and that it is as toxicologically active as the parent c ompound. (C) 1997 Elsevier Science Ltd.