Pathophysiology and Toxicokinetic Studies of Blue-Green Algae Intoxication in the Swine Model
Abstract
Microcystin LR (MCLR) was stable in aqueous solution for up to several days. Stability was enhanced at low temperatures. Reversed phase high performance liquid chromatography and thin layer chromatography are effective for characterizing MCLR purity. ODS-silica gel extraction, and silica gel column chromatography with HPLC and UV detection at 238 nm are effective for toxin purification. Rat hepatocytes exposed in vitro to MCLR developed marked blebbing of the plasma membrane whereas nonparenchymal cells (Kupffer and endothelial cells) did not. Rat hepatocytes were affected by MCLR in vivo before sinusoidal endothelial cells; there is an early loss of hepatocyte microvilli and invagination of the plasma membrane; plasma membranes are distorted or lost before marked changes in organelles or the nucleus; hepatocytes and debris pass into small arterioles and capillaries of the lungs and peripheral circulation including renal capillaries. Rhodamine labelled phalloidin staining and fluorescence microscopy with primary cultures of rat hepatocytes and livers of dosed rats revealed marked disorganization of the actin microfilaments of the hepatocyte cytoskeleton. In mice dosed IP, a toxic dose of MCLR induced tolerance to a subsequent 'consistently lethal' dose. Livers of survivors displayed hepatocyte regeneration. Gut loop administration of MCLR in vivo, provided evidence for greater uptake from ileum than jejunum. Cholestyramine bound and decreased the toxicity of MCLR in rats dosed via ileal loops: activated charcoal was effective in vitro, but less so in vivo, apparently due to precipitation.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 26, 1991
- Accession Number
- ADA244902
Entities
People
- Andrew M. Dahlem
- Val R. Beasley
- Wanda M. Haschek-hock
- Wayne M. Carmichael
- William O. Cook
Organizations
- University of Illinois Urbana–Champaign