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Microcystins:
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Symptoms and Treatment, Toxicity,
Chemistry, Site of Action,
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| Symptoms, Treatment, Decontamination | |
| Syndrome Name | None |
| Symptoms |
Microcystins are hepatotoxic, causing necrosis and pooling of blood in the liver with the organ gaining up to 100% of its normal weight. |
| Onset of Symptoms | Rapid, with death occurring in a few hours if a lethal dose is taken. |
| Rapid diagnostic assay | A number of sensitive assays, including an ELISA, a fluorimetric assay, enzyme inhibition assays, and assays for breakdown products have been described. Commercial test kits are available from Strategic Diagnostics and Abraxis. |
| Antidote | None. |
| Supportive Care | Damage to the liver is rapid and irreversible. Dialysis or liver transplants may be the only effective treatments. The antibiotic rifampin shows protective effects in animal studies and could be used prophylactically if a genuine threat of an attack exists. |
| Inactivation | Microcystins are stable in water, air and strong sunlight. They may be inactivated by high levels of chlorine during water purification. |
For microcystin LR, the most toxic of the microcystins, the LD50 for rats and mice are in the range 36-122 micrograms/kg with the inhalation toxicity 180 mg/min/m3 or 43 micrograms/kg. The LD0 or highest dose having no toxic effect is about 25 micrograms/kg and, depending upon the route of administration, the LD100 or dose guaranteed to kill can be as low as 40 micrograms/kg. There is considerable variation in sensitivity to microcystins aming animals with horse being more sensitive than rats or mice and dogs being significantly more resistant.
The site of action of microcystins is the hepatocyte, the commonest cell type in the liver. They act by disrupting the cytoskeleton, the adaptable protein framework that constantly shapes and reshapes the cell as it responds to the environment. The cells die and this destroys the finer blood vessels of the liver leading to massive hepatic bleeding.
The molecular target are a group of enzymes called protein phosphatases that play a role in regulating protein interactions and activities. Very well-defined types of protein phosphatase (type 1 and type 2A) are inhibited very specifically by very low concentrations of microcystins. Microcystins also activate the enzyme phosphorylase b, which plays a very important role in the affairs of the hepatocyte. The combination of inhibition and activation is rapidly lethal to the cell. The specificity of some of these toxins makes them valuable research tools.
Species of the cyanobacterium or blue-green alga Microcystis, particularly M. aeruginosa. This organism is a public health concern because it can grow rapidly in water rich in organic matter during warm weather during the phenomenon of "algal blooms" the green filamentous masses found floating on the surface of water. The toxin concentrations in a M. aeruginosabloom can quickly exceed safe levels. It is difficult for anyone except an expert to identify these microorganisms, so all algal blooms have to be treated as potentially hazardous.
Microcystins are about as toxic as G-type nerve agents. The producer organisms can be fairly easily cultured and manufacturing the toxin should present no insuperable technical difficulties.
| Disease | ICD-9-CM | ICD-10 |
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