Mechanisms of microcystin-LR toxicity

Microcystin-LR (MCLR) is a cyanobacterial hepatotoxin that inhibits serine/threonine protein phosphatases types 1 and 2A in hepatocytes in vivo and in vitro, and disrupts actin microfilament (MF), microtubule (MT) and intermediate filament (IF) networks. The sequential ultrastructural and biochemical changes induced by MCLR were studied in the isolated perfused rat liver model. Livers were perfused with doses ranging from 0.1 to 5.0 μg/ml for 5 to 40 min in order to characterize the earliest observable morphologic changes presumably induced by disorganization of the hepatocyte cytoskeleton, and to follow the progression of lesions over time. The earliest toxin-induced changes were observed at 0.1 μg/ml after 15-20 min exposure, or at 0.3 μg/ml after 5-10 min. Earliest lesions included loss of hepatocyte microvilli, widening of sinusoidal fenestrae with disruption of sinusoidal endothelium, dilation of bile canaliculi, widening of intercellular spaces, and the initial stages of hepatocyte separation. Lesions progressed in severity and extent with increasing dose and exposure time. The observed changes are likely to be attributable in large measure to altered hepatocyte cytoskeletal structure and function.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Veterinary Medical Science

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2011

Author dc:creator

• Wickstrom, Mark Lee

Contributors dc:contributor

• Beasley, Val Richard

• Health Sciences, Toxicology
• Agriculture, Animal Pathology
• Health Sciences, Pathology
• Biology, Veterinary Science

Statement dc:rights

• Copyright 1996 Wickstrom, Mark Lee

Language dc:language

eng

Identifier

9780591089103
AAI9702713
(UMI)AAI9702713

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/19369