Isolated rat liver perfusion studies with cyclic heptapeptide toxins of Microcystis and Oscillatoria (freshwater cyanobacteria)

Berg, Kjetil; Wyman, John F.; Carmichael, Wayne W.; Dabholkar, Arun S.

doi:10.1016/0041-0101(88)90324-8

Cited by 28 publications

(7 citation statements)

References 12 publications

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“…MCs led to the formation of digestive vacuoles in cytoplasm, fusion of lysosomes, swelling of the ER and vacuolization of the Golgi apparatus. This is consistent with the results of other studies that have found that ER in hepatic cells of rats and carp were the most sensitive organelle when exposed to crude MC-LR extracted from CBE (Berg et al 1988;Li et al 2001). The results of those studies suggested that the structural deformations were related to modifications of the cytoskeleton.…”

Section: Discussionsupporting

confidence: 95%

Genotoxicity of crude extracts of cyanobacteria from Taihu Lake on carp (Cyprinus carpio)

Gao

et al. 2011

Ecotoxicology

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Genotoxicity of crude cyanobacteria extracts (CBE) from blooms in Taihu Lake, China toward common carp (Cyprinus carpio) was measured. The primary extracellular product was determined by HPLC to be Microcystin-LR (MC-LR, L for leucine and R for arginine) with an average concentration of 2.4 × 10(2) μg MC g(-1) dry weight of cyanobacteria. Acute toxicity to carp, expressed as the 72-h LC(50,) was 53 mg, dw cyanobacteria L(-1). Genotoxicity, as determined by the micronucleus (MN) and comet assays were both dose- and time-depended. Deformities of cellular organelles in liver and gill were observed by use of transmission electron microscopy (TEM). The results showed that MC-LR from cyanobacteria from Taihu Lake could induce genotoxic response and tissue-level morphological changes in common carp.

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Section: Discussionsupporting

confidence: 95%

Genotoxicity of crude extracts of cyanobacteria from Taihu Lake on carp (Cyprinus carpio)

Gao

et al. 2011

Ecotoxicology

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“…In addition, in control livers, there were no ultrastructural changes consistent with hypoxic injury, the hallmarks of which include loss of microvilli, cytoplasmic vacuolization, and mitochondria1 swelling [Schmucker and Curtis, 1974;Schmucker et al, 19751. The lack of release of cytosolic enzymes from hepatocytes in response to MCLR in the present study is consistent with previous reports involving exposure of isolated perfused livers or hepatocyte suspensions to a purified microcystin, in which enzyme release or Trypan blue uptake were used as a biomarker of plasma membrane damage [Berg et al, 1988Runnegar et al, 1995;Runnegar and Falconer, 19821. Thus, it appears that, in isolated livers perfused with MCLR, hepatocyte plasma membranes tend to remain intact.…”

Section: Petfusate Biochemical Parameterssupporting

confidence: 92%

Sequential ultrastructural and biochemical changes induced by microcystin-LR in isolated perfused rat livers

et al. 2006

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The cyanobactenal hepatotoxin, microcystin‐LR (MCLR), is a potent protein phosphatase inhibitor that disrupts actin microfilament, cytokeratin intermediate filament, and microtubule networks in hepatocytes. To determine ultrastructural and biochemical changes that develop concurrently with microcystin‐induced cytoskeletal disorganization, isolated rat livers were perfused with MCLR at 0.1 to 5.0 μg/ml for 5 to 40 min. Lactate dehydrogenase, alanine aminotransferase, and aspartate aminotransferase changed over time, but trends for toxin‐treated and control livers did not differ. The earliest toxin‐induced ultrastructural changes, observed in livers perfused at 0.1 μg/ml for 15–20 min or at 0.3 μg/ml for 5–10 min, were loss of hepatocyte microvilli in the space of Disse, widening of sinusoidal fenestrae, disruption of sinusoidal endothelium, dilation of bile canaliculi with loss of microvilli, and widening of hepatocyte intercellular spaces. Lesions progressed with increasing toxin concentrations and exposure times. In livers perfused with MCLR at 0.5 μg/ml for 10–20 min, hepatocytes had plasma membrane blebs and concentric whorls of rough endoplasmic reticulum, and there was marked disassociation of hepatocytes resulting in disrupted hepatic cords. At toxin concentrations of 2.0 or 5.0 μg/ml for 10–20 min, there was mild dilation of mitochondrial cristae, cytoplasmic vacuolization or invagination of plasma membranes, redistribution of organelles, and sometimes nuclear degenerative change. Some hepatocytes exhibited clusters of plasma membrane blebs radiating from round cytoplasmic structures, which may be composed primarily of condensed microfilaments.

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“…Hepatotoxic effects of MCYST have been studied in isolated hepatocytes, both in suspension (Runneqar et al, 1987) and 13 monolayers (Thompson et al, 1987), perfused livers (Berg et al, 1988) and several whole animal models (Konst et al, 1965;Jackson at al., 1984;and Miura et al, 1988). The isolated perfused liver has several advantages over other model systems for the study of hepatotoxins.…”

Section: Discussionmentioning

confidence: 99%

Toxicity and kinetics of [3H]microcystin-LR in isolated perfused rat livers

Pace

Robinson

Miura

et al. 1991

Toxicology and Applied Pharmacology

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Isolated rat liver perfusion studies with cyclic heptapeptide toxins of Microcystis and Oscillatoria (freshwater cyanobacteria)

Cited by 28 publications

References 12 publications

Genotoxicity of crude extracts of cyanobacteria from Taihu Lake on carp (Cyprinus carpio)

Genotoxicity of crude extracts of cyanobacteria from Taihu Lake on carp (Cyprinus carpio)

Sequential ultrastructural and biochemical changes induced by microcystin-LR in isolated perfused rat livers

Toxicity and kinetics of [3H]microcystin-LR in isolated perfused rat livers

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