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Pathophysiology of cyanoginosin-LR: in vivo and in vitro studies
W H Adams1, J P Stone, B Sylvester
1Medical Department, Brookhaven National Laboratory, Upton, New York 11973.
Abstract:
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.
Insights
Cyanoginosin-LR, a potent toxin from Microcystis aeruginosa, causes rapid death in mice by damaging liver sinusoidal endothelium, leading to hemorrhage and cell embolization. Its mechanism involves vascular damage, not direct liver cell failure.
Area of Science:
- Toxicology
- Hepatology
- Microbiology
Background:
- Cyanoginosin-LR is a cyclic heptapeptide toxin produced by Microcystis aeruginosa.
- It is known to be highly virulent, causing rapid mortality in animal models.
Purpose of the Study:
- To investigate the mechanism of rapid lethality induced by cyanoginosin-LR.
- To identify the primary target organ and cellular damage caused by the toxin.
Main Methods:
- Intravenous and intraperitoneal injection of cyanoginosin-LR in mice.
- Histopathological examination of liver and lung tissues.
- In vitro studies on endothelial cells and macrophages.
- Measurement of plasma fibronectin, thromboxane B2, and 6-keto-prostaglandin F1 alpha levels.
Main Results:
- Cyanoginosin-LR caused rapid death, characterized by disintegration of sinusoidal endothelium and massive intrahepatic hemorrhage.
- No direct injury to endothelial cells or macrophages was observed in vitro.
- Transient increase in plasma fibronectin and elevated levels of thromboxane B2 and 6-keto-prostaglandin F1 alpha were noted.
- Acute thrombocytopenia was observed but its cause remained unexplained.
Conclusions:
- The rapid lethality of cyanoginosin-LR is primarily mediated by damage to the hepatic sinusoidal endothelium, leading to hemorrhage and potential cell embolization.
- The toxin's effects share similarities with lipopolysaccharide endotoxins.
- Further research is needed to elucidate the mechanism behind the observed thrombocytopenia.
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