Blood pressure and hepatocellular effects of the cyclic heptapeptide toxin produced by the freshwater cyanobacterium (blue-green alga) Microcystis aeruginosa strain PCC-7820.

Laboratory rats and mice were used to investigate the hepatotoxicity caused by the cyclic heptapeptide (mol. wt 994) termed microcystin-LR. Microcystin-LR (also known as cyanoginosin-LR) is produced by the freshwater cyanobacterium (blue-green alga) M. aeruginosa strain PCC-7820. In time course histopathology studies with mice significant liver damage, with an absence of pulmonary emboli, were observed after 15 min. Pulmonary emboli did not appear until 1 hr. In rats, significant liver damage and the presence of occasional emboli were observed at 20 min. Pulmonary emboli did not contain fibrin nor appear life-threatening in any case and resembled the globular eosinophilic debris found in the liver sinusoids and central veins. Measurements of rat femoral arterial, jugular venous and hepatic portal venous blood pressures during the course of toxicity revealed a slowly declining arterial pressure and stable, normal venous pressures. Blood lactic acid levels rose in parallel with the fall in arterial pressure, a pattern typical of hemorrhagic shock. There was no indication of venous congestion that would accompany right heart failure. Isolated, perfused rat livers dosed with toxin showed rapid changes in the liver, including cessation of bile flow within 10 min and complete obliteration of normal lobular architecture within 60 min. No effect of the toxin was observed in isolated perfused rat heart. We conclude that in the mouse and rat, microcystin-LR is a potent, rapid-acting, direct hepatotoxin, with the immediate cause of death in acute toxicities being hemorrhagic shock secondary to massive hepatocellular necrosis and collapse of hepatic parenchyma.