Structure/toxicity relationships and fate of low molecular weight peptide toxins from cyanobacteria

Hepatic glutathione (GSH) was depleted to assess the influence of GSH on the toxicity of MCYST-LR in vivo. The GSH conjugate of MCYST-LR was also formed synthetically. There was an approximately four-fold decrease in the toxicity of the GSH derivative, as compared to the parent toxin; but the GSH conjugate remained hepatotoxic and hepatospecific in its effects. Tritium-labeled sodium borohydride was used to produced tritium-labeled 2H-MCYST-LR. The labeled toxin was administered intraperitoneally to male mice in lethal or sublethal doses, and the organ distributions measured over a 60 min observation period. Sublethal doses were also administered to a second group of mice and the excretion of radioactivity in urine and feces was measured at 12 hr intervals for 72 hr, along with tissue distribution at the end of the observation period. Accumulation of labeled toxin in the livers of treated animals was rapid with 94.7 ± 3.3% (mean ± S.D.) of the sublethal dose present in the liver after 1 hr, and 57.8 ± 5.2% of the administered dose present 72 hr after administration. The small intestine also accumulated radioactivity in both treatment groups. Excretion of the toxin in sublethally dosed animals occurred primarily via the feces