Comparison of in vivo and in vitro toxic effects of microcystin-LR in fasted rats

G. A. Miura, N. A. Robinson, Thomas Geisbert, K. A. Bostian, J. D. White, J. G. Pace

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

G. A. Miura, N. A. Robinson, T. W. Geisbert, K. A. Bostian, J. D. White and J. G. Pace. Comparison of in vivo and in vitro toxic effects of microcystin-LR in fasted rats. Toxicon27, 1229-1240, 1989.-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 μg/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.

Original languageEnglish (US)
Pages (from-to)1229-1240
Number of pages12
JournalToxicon
Volume27
Issue number11
DOIs
StatePublished - 1989
Externally publishedYes

Fingerprint

Mitochondria
Poisons
Rats
Desmosomes
Intermediate Filaments
Cytoskeleton
Edema
L-Iditol 2-Dehydrogenase
Microcystis
Electrons
Subcellular Fractions
Rough Endoplasmic Reticulum
Liver Mitochondrion
Rat control
Cyanobacteria
Electron Transport
Dilatation
Hepatocytes
Cell membranes
Cell Membrane

ASJC Scopus subject areas

  • Toxicology

Cite this

Miura, G. A., Robinson, N. A., Geisbert, T., Bostian, K. A., White, J. D., & Pace, J. G. (1989). Comparison of in vivo and in vitro toxic effects of microcystin-LR in fasted rats. Toxicon, 27(11), 1229-1240. https://doi.org/10.1016/0041-0101(89)90031-7

Comparison of in vivo and in vitro toxic effects of microcystin-LR in fasted rats. / Miura, G. A.; Robinson, N. A.; Geisbert, Thomas; Bostian, K. A.; White, J. D.; Pace, J. G.

In: Toxicon, Vol. 27, No. 11, 1989, p. 1229-1240.

Research output: Contribution to journalArticle

Miura, GA, Robinson, NA, Geisbert, T, Bostian, KA, White, JD & Pace, JG 1989, 'Comparison of in vivo and in vitro toxic effects of microcystin-LR in fasted rats', Toxicon, vol. 27, no. 11, pp. 1229-1240. https://doi.org/10.1016/0041-0101(89)90031-7
Miura, G. A. ; Robinson, N. A. ; Geisbert, Thomas ; Bostian, K. A. ; White, J. D. ; Pace, J. G. / Comparison of in vivo and in vitro toxic effects of microcystin-LR in fasted rats. In: Toxicon. 1989 ; Vol. 27, No. 11. pp. 1229-1240.
@article{4d6321a41ac74636a02b5d02f530cdc5,
title = "Comparison of in vivo and in vitro toxic effects of microcystin-LR in fasted rats",
abstract = "G. A. Miura, N. A. Robinson, T. W. Geisbert, K. A. Bostian, J. D. White and J. G. Pace. Comparison of in vivo and in vitro toxic effects of microcystin-LR in fasted rats. Toxicon27, 1229-1240, 1989.-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 μg/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.",
author = "Miura, {G. A.} and Robinson, {N. A.} and Thomas Geisbert and Bostian, {K. A.} and White, {J. D.} and Pace, {J. G.}",
year = "1989",
doi = "10.1016/0041-0101(89)90031-7",
language = "English (US)",
volume = "27",
pages = "1229--1240",
journal = "Toxicon",
issn = "0041-0101",
publisher = "Elsevier Limited",
number = "11",

}

TY - JOUR

T1 - Comparison of in vivo and in vitro toxic effects of microcystin-LR in fasted rats

AU - Miura, G. A.

AU - Robinson, N. A.

AU - Geisbert, Thomas

AU - Bostian, K. A.

AU - White, J. D.

AU - Pace, J. G.

PY - 1989

Y1 - 1989

N2 - G. A. Miura, N. A. Robinson, T. W. Geisbert, K. A. Bostian, J. D. White and J. G. Pace. Comparison of in vivo and in vitro toxic effects of microcystin-LR in fasted rats. Toxicon27, 1229-1240, 1989.-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 μg/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.

AB - G. A. Miura, N. A. Robinson, T. W. Geisbert, K. A. Bostian, J. D. White and J. G. Pace. Comparison of in vivo and in vitro toxic effects of microcystin-LR in fasted rats. Toxicon27, 1229-1240, 1989.-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 μg/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.

UR - http://www.scopus.com/inward/record.url?scp=0024468947&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0024468947&partnerID=8YFLogxK

U2 - 10.1016/0041-0101(89)90031-7

DO - 10.1016/0041-0101(89)90031-7

M3 - Article

VL - 27

SP - 1229

EP - 1240

JO - Toxicon

JF - Toxicon

SN - 0041-0101

IS - 11

ER -