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https://hdl.handle.net/2142/19889
Description
Title
The toxicity of microcystin-LR in swine and mice
Author(s)
Lovell, Randall Anderson
Issue Date
1989
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)
Biology, Animal Physiology
Health Sciences, Pathology
Biology, Veterinary Science
Language
eng
Abstract
Microcystin-LR (MCLR) is a monocyclic heptapeptide hepatotoxin produced by the cyanobacterium Microcystis aeruginosa. One gilt given whole M. aeruginosa cells ig containing 0.3% MCLR and des-methyl MCLR at 2.1 g/kg had severe panlobular hepatic necrosis and hemorrhage when euthanatized at 32.5 hr postdosing.
Mean liver and kidney weights increased 50-64% and 20-32%, respectively, in two strains of male mice that died within 200 minutes after a single lethal ip dose of purified MCLR. Mice that survived an ip LD$\sb{23}$ or LD$\sb{30}$ of MCLR had significantly longer survival times and higher survival rates when given an approximate ip LD$\sb{100}$ minimum (40-75 $\mu$g/kg) 2 or 3 days later.
The liver (34.01 IU/g), pancreas (5.43 IU/g), and kidney (3.24 IU/g) were the only swine tissues with mean arginase activity (ARG) greater than 0.52 IU/g. The serum t${1\over2}$ of ARG in a barrow and gilt were 85.8 and 128.0 minutes (min).
Between 12 and 24 min after anesthetized gilts were given a lethal iv dose of purified MCLR (72 $\mu$g/kg), mean aortic and central venous pressures, and renal and hepatic perfusion decreased ($\downarrow$) significantly, while portal venous pressure increased ($\uparrow$) significantly. Significant changes at 45 min included $\uparrow$ bile acids, total bilirubin, lactate, K, and pO$\sb2$, and $\downarrow$ platelet count, base excess, Hct, HCO$\sb3-$, and pCO$\sb2$. At 90 min, significant changes included $\uparrow$ ARG, P, BUN, and creatinine, and $\downarrow$ pH and glucose. Significant changes 150 min postdosing included $\uparrow$ AST, AP, ALT, CPK, and LDH. Livers were markedly enlarged, dark purple-red in color, and readily exuded blood on cut surfaces. Significantly $\uparrow$ liver weights and liver Fe and Hb concentrations were suggestive that 37.9% of the estimated blood volume was present in the liver. The major cause of acute death ($<$5 hr) following iv MCLR dosing in swine is hypovolemic shock which results from massive intrahepatic hemorrhage.
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