title: Comparison of in vivo and in vitro toxic effects of microcystin-LR in fasted rats.
abstract: The toxic effects of microcystin-LR, a cyclic heptapeptide isolated from the cyanobacterium 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 15-90 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. The 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 to 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 a cascade of events not supported in in vitro models.
authors.affiliation: Pathophysiology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland 21701-5011.
authors.forename: G A
authors.initials: GA
authors.lastname: Miura
authors.forename: N A
authors.initials: NA
authors.lastname: Robinson
authors.forename: T W
authors.initials: TW
authors.lastname: Geisbert
authors.forename: K A
authors.initials: KA
authors.lastname: Bostian
authors.forename: J D
authors.initials: JD
authors.lastname: White
authors.forename: J G
authors.initials: JG
authors.lastname: Pace
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004579:Electron Transport; D004591:Electrophoresis, Polyacrylamide Gel; D005215:Fasting / Q000502:physiology*; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D008387:Marine Toxins; D052998:Microcystins; D008854:Microscopy, Electron; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D010456:Peptides, Cyclic / Q000633:toxicity*; D051381:Rats
chemical_list: D008387:Marine Toxins; D052998:Microcystins; D010456:Peptides, Cyclic; D000244:Adenosine Diphosphate; C057862:cyanoginosin LR