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

The toxicokinetics of tritiated dihydromicrocystin-LR ( ($\sp3$H) 2H-MCLR) were studied in anesthetized pigs. Two dose groups (75 and 25 μg/kg) were given radiolabeled plus nonlabeled 2H-MCLR IV and one dose group (75μg/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 μg/kg dose was slower than at the 25 μg/kg dose. Following administration of ($\sp3$H) 2H-MCLR at 75 μg/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 μg/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 μg/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 μg/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.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Veterinary Biosciences

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2011

Author dc:creator

• Stotts, Richard Rae

Contributors dc:contributor

• Beasley, Val Richard

• Health Sciences, Toxicology
• Biology, Microbiology
• Biology, Veterinary Science

Statement dc:rights

• Copyright 1996 Stotts, Richard Rae

Language dc:language

eng

Identifier

AAI9625200
(UMI)AAI9625200

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/20389