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

Natural Toxins
M L WickstromV R Beasley

Abstract

The cyanobacterial 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 micrograms/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 microgram/ml for 15-20 min or at 0.3 microgram/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 microgram/ml for 10-20 min, hepatocytes had plasma membrane blebs and concentric whorls of rough endoplasmic reticulum, and there was marked disassociation of...Continue Reading

Citations

Mar 4, 2000·Environmental Health Perspectives·B C HitzfeldD R Dietrich
Jun 26, 2014·Environmental Toxicology·Shangchun LiLiang Chen
Jul 10, 1998·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·D M ToivolaJ E Eriksson
Mar 7, 2014·Toxicon : Official Journal of the International Society on Toxinology·L J MattosR M Soares
Jul 2, 2008·Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP·Yanyan ZhaoDapeng Li

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