Comparison of In-Vitro and In-Vivo Toxic Effects of Microcystin-LR in Fasted Rats
Abstract
The toxic effects of microcystin-LR, a cyclic heptapeptide isolated from the blue-green alga Microcystis aeruginosa, were studied in the fasted rat model and in subcellular fractions from fasted, toxin-treated and control rats. Hepatotoxic effects of a lethal dose (100 micrograms/kg) were examined 15 to 90 min post-injection. Elevations of serum enzymes, particularly sorbitol dehydrogenase, specific for liver mitochondria, correlated with hepatic damage. Electron micrographs showed progressive cellular disruption, including dilation of rough endoplasmic reticulum, incorporation of cellular components into cytolysosomes, hydropic mitochondria devoid of electron-opaque deposits, loss of desmosome-associated intermediate filaments, disruption of sinusoidal architecture, and ultimately lysis of hepatocytes. Appearance of hydropic mitochondria correlated with loss of coupled electron transport. Changes in plasma membrane-associated cytoskeletal filaments correlated with loss of desmosome tonofilaments. In contrast to in-vivo exposure microcystin-LR, in- vitro exposure to toxin had no effect on mitochondria or cytoskeletal filaments, suggesting that the toxic effects observed in-vivo were indirect and may be dependent on bioactivation of the toxin or cascade of events not supported in in-vitro models.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 15, 1989
- Accession Number
- ADA208928
Entities
People
- George A. Miura
- John D. White
- Karen A. Bostian
- Nancy A. Robinson
- Thomas W Geisbert
Organizations
- United States Army Medical Research Institute of Infectious Diseases