Synthesis, organotropism and hepatocellular uptake of two tritium-labeled epimers of dihydromicrocystin-LR, a cyanobacterial peptide toxin analog.

Abstract J. A. O. Meriluoto , S. E. Nygard , A. M. Dahlem and J. E. Eriksson . Synthesis, organotropism and hepatocellular uptake of two tritium-labeled epimers of dihydromicrocystin-LR, a cyanobacterial peptide toxin analog. Toxicon , 28, 1439–1446, 1990.—Two tritium-labeled epimers of dihydromicrocystin-LR, a derivative of the cyanobacterial peptide hepatotoxin microcystin-LR, were synthesized by reduction with sodium boro[ 3 H]hydride and purified with reversed-phase liquid chromatography. The epimers were hepatotoxic in mice; the i.p. ld 50 was 120–135 μg/kg. They were concentrated in the liver and to some extent in the intestine and the kidney after an i.v. injection. Freshly isolated rat hepatocytes showed a rapid uptake of both epimers. The cellular uptake of the epimers was almost complete within 5 min at concentrations 1 μM (0.5 μM dihydromicrocystin - LR + 0.5 μM microcystin - LR ) and 4 μM (0.5 μM + 3.5 μM ). The uptake of the earlier eluting epimer was about three times higher than that of the later eluting epimer.