Effect of Microcystin-LR on Cultured Rat Endothelial Cells
Abstract
Microcystin-LR, a polypeptide synthesized by the cyanobacterium Microcystis aerugenosa, induces hepatotoxicity in many species including man. After administration to laboratory rodents, microcystin-LR rapidly induces severe liver hemorrhage, which is associated with centrilobual hepatocyte necrosis. Microsystin-LR also induces necrosis of cultured rat hepatocytes after several hours of incubation with the toxin. The mechanism by which microcystin- LR induces hepatotoxicity is not known. Microcystin-LR effects do not appear to be mediated by the inhibition of macromolecular biosynthesis; i.e. protein, RNA or DNA synthesis. Microcystin-LR induces early changes in cultured hepatocytes, such as cell deformation (blebbing), rapid rise in intracellular calcium, increased phosphorylase-a activity, depletion of glutathione and the release of arachidonic acid metabolites. These early events were followed by the leakage of adenine nucleotides and, cytoxolic enzymes and eventually, the loss of cell viability. Microcystin-LR toxicity to cultured hepatocytes has been well documented but relatively little is known about its effects on other nonparenchymal liver cells, that is, sinusoidal endothelial and Kupffer cells. In the present study, we investigated the effects of microcystin-LR on cultured primary liver endothelial cells. Keywords: Physiological effects, Toxins.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 10, 1989
- Accession Number
- ADA205492
Entities
People
- G. W. Anderson Jr.
- J. Hewetson
- K. Mereish
- R. Solow
Organizations
- United States Army Medical Research Institute of Infectious Diseases