Pathophysiology of cyanoginosin-LR: in vivo and in vitro studies.
Cyanoginosin-LR, one of the group of virulent cyclic heptapeptide toxins (cyanoginosins) isolated from some strains of the cyanobacterium, Microcystis aeruginosa, kills mice within 1-2 hr after iv or ip injection. Although the liver is a target organ of the toxin, the rapidity of lethality is incompatible with metabolic death from failure of hepatocellular function. However, disintegration of sinusoidal endothelium causes massive intrahepatic hemorrhage. The loss of the structural integrity of hepatic sinusoids provides a previously undescribed mechanism for embolization of disintegrating cells from the liver to the lung. No injury to either cultured bovine pulmonary artery endothelial cells or mouse peritoneal macrophages was observed following prolonged incubation with high concentrations of the toxin, and there was no increase in vascular permeability to 125I-labeled albumin detected before intrahepatic hemorrhage. However, plasma fibronectin increased transiently after toxin injection. Acute, severe thrombocytopenia, a characteristic of cyanoginosin-LR toxicity, remains unexplained since platelets did not concentrate in the lungs, liver, or spleen. There are similarities between the effects of cyanoginosin-LR and of the lipopolysaccharide endotoxins, such as elevations of plasma levels of thromboxane B2 and 6-keto-prostaglandin F1 alpha.
Adams
W H
WH
Medical Department, Brookhaven National Laboratory, Upton, New York 11973.
Stone
J P
JP
Sylvester
B
B
Stoner
R D
RD
Slatkin
D N
DN
Tempel
N R
NR
Siegelman
H W
HW
D000818:Animals; D005353:Fibronectins / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008168:Lung / Q000187:drug effects; D008387:Marine Toxins; D051379:Mice; D052998:Microcystins; D008854:Microscopy, Electron; D010456:Peptides, Cyclic / Q000633:toxicity*; D013921:Thrombocytopenia / Q000139:chemically induced
D005353:Fibronectins; D008387:Marine Toxins; D052998:Microcystins; D010456:Peptides, Cyclic; C057862:cyanoginosin LR