Toxicokinetics and structure/toxicity relationships of low molecular weight peptide toxins from cyanobacteria
Stotts, Richard Rae
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Permalink
https://hdl.handle.net/2142/20389
Description
Title
Toxicokinetics and structure/toxicity relationships of low molecular weight peptide toxins from cyanobacteria
Author(s)
Stotts, Richard Rae
Issue Date
1996
Doctoral Committee Chair(s)
Beasley, Val Richard
Department of Study
Veterinary Biosciences
Discipline
Veterinary Biosciences
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Health Sciences, Toxicology
Biology, Microbiology
Biology, Veterinary Science
Language
eng
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.
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