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Toxicokinetics and structure/toxicity relationships of low molecular weight peptide toxins from cyanobacteria

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Title: Toxicokinetics and structure/toxicity relationships of low molecular weight peptide toxins from cyanobacteria
Author(s): Stotts, Richard Rae
Doctoral Committee Chair(s): Beasley, Val R.
Department / Program: Veterinary Biosciences
Discipline: Veterinary Biosciences
Degree Granting Institution: University of Illinois at Urbana-Champaign
Degree: Ph.D.
Genre: Dissertation
Subject(s): Health Sciences, Toxicology Biology, Microbiology Biology, Veterinary Science
Abstract: The toxicokinetics of tritiated dihydromicrocystin-LR ( ($\sp3$H) 2H-MCLR) were studied in anesthetized pigs. Two dose groups (75 and 25 $\mu$g/kg) were given radiolabeled plus nonlabeled 2H-MCLR IV and one dose group (75$\mu$g/kg) was given radiolabeled plus nonlabeled 2H-MCLR via an isolated ileal loop. At either IV dose, more than half the radiolabel from ($\sp3$H) 2H-MCLR present in the blood at one minute postdosing was cleared by 6 minutes. The blood clearance at the 75 $\mu$g/kg dose was slower than at the 25 $\mu$g/kg dose. Following administration of ($\sp3$H) 2H-MCLR at 75 $\mu$g/kg via the ileum, the maximal concentration of toxin in blood was achieved at 90 minutes after dosing, when ($\sp3$H) 2H-MCLR in portal venous blood was 3.6 times higher than in peripheral venous blood. At 4 hours after IV dosing at 25 $\mu$g/kg, 64.6 percent of the total dose (%TD) was located in the liver tissue, with lesser amounts in the kidneys (1.2%TD), lungs (1.75%TD), heart (0.22%TD), ileum (0.13%TD), and spleen (0.04%TD). A similar distribution in pigs was found at 4 hours after dosing IV at 75 $\mu$g/kg, with the liver containing somewhat less at 46.99%TD, and the kidneys containing slightly more at 2.19%TD. The livers of the pigs given 75 $\mu$g/kg via the ileal loop at 5 hours postdosing, contained 49.5%TD and the ileum had 33.94%TD. The majority of radiolabel in the liver could be accounted for by parent compound, but two minor radioactive components were also isolated.The relative toxicity of microcystins from a cyanobacterial bloom containing Microcystis aeruginosa, M. viridis, and M. wesenbergii, was studied. Ten hepatotoxic microcystins and one microcystin, a laboratory breakdown product, of substantially reduced toxicity were isolated. The compound with reduced toxicity, was nonlethal at 1 mg/kg (IP mouse) and was determined to have a (C$\rm\sb3H\sb7O\sb2$) mono-ester of the alpha-carboxyl on the Glu unit of microcystin-LR. The other nine microcystins had approximate LD$\sb{50}$s ranging from 97 $\mu$g/kg to 750 $\mu$g/kg.
Issue Date: 1996
Type: Text
Language: English
URI: http://hdl.handle.net/2142/20389
Rights Information: Copyright 1996 Stotts, Richard Rae
Date Available in IDEALS: 2011-05-07
Identifier in Online Catalog: AAI9625200
OCLC Identifier: (UMI)AAI9625200
 

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