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Title:Pathophysiologic effects of anatoxin-a(s), a toxin from the cyanobacterium Anabaena flos-aquae
Author(s):Cook, William Oscar, II
Doctoral Committee Chair(s):Beasley, Val Richard
Department / Program:Biology, Veterinary Science
Discipline:Biology, Veterinary Science
Degree Granting Institution:University of Illinois at Urbana-Champaign
Subject(s):Biology, Veterinary Science
Abstract:Extracts containing anatoxin-a(s) (antx-a(s)) or purified antx-a(s) from Anabaena flos-aquae NRC 525-17 were evaluated for effects on brain (whole brain or cortex, medulla, midbrain, hippocampus, hypothalamus, olfactory lobes, striatum, and the anterior cervical spinal cord) cholinesterase (ChE) in vivo after parenteral administration to mice, rats, and swine. Antx-a(s) did not inhibit ChE in these tissues, but did cause clinical signs, inhibition of plasma, red blood cell (RBC) and/or whole blood ChE, and lethality, suggesting that the toxin is unable to cross the blood brain barrier and is strictly an inhibitor of peripheral ChE. A similar pattern of ChE inhibition was observed in mice, swine, ducks, and a steer given extracts of 3 different algal blooms containing ChE-inhibiting toxin(s).
When the reversibility of inhibition of plasma, RBC, and diaphragm ChE by antx-a(s) was examined in vivo using mice, antx-a(s) was found to be an irreversible inhibitor of ChE.
The effects of antx-a(s) on arterial blood pressure (BP), heart rate (HR), respiratory rate (RR), tidal volume (TV), minute volume (MV), integrated phrenic nerve (PN) activity, and diaphragm electromyographic (EMG) activity were evaluated in anesthetized rats. Marked decreases in HR and BP frequently occurred prior to a large decrease in MV, suggesting that antx-a(s) had an important muscarinic action on the cardiovascular (CV) system. PN amplitude increased despite a progressive decrease in TV and MV, indicating that antx-a(s) did not profoundly inhibit central respiratory drive. Diaphragm EMG decreased markedly prior to death suggesting toxin-induced neuromuscular blockade in vivo. Rats pretreated with atropine sulfate survived significantly longer than rats given toxin alone, and decreases in HR and BP followed a decrease in TV and MV, suggesting that neuromuscular blockade of the muscles of respiration was the cause of death. Rats that were ventilated and not given atropine survived more than 4 fold the consistently lethal dose of antx-a(s), indicating that the CV effects of antx-a(s) alone were insufficient to cause death.
Rats dosed with antx-a(s) were evaluated for neurobehavioral effects with accelerod (AR), figure 8 maze (F8M), grip strength (GS), and startle response (SR) equipment. Dose dependent deficits were detected in AR, F8M, and SR tests, but not in the GS test. Significant decrements were observed only at a relatively high dose (28% of the LD50), which caused clinical signs. Despite irreversible inhibition of ChE by the toxin, the behavioral effects appeared to be reversible within 48 hours. Such observations are compatible with the toxin only having peripheral activity.
Issue Date:1989
Rights Information:Copyright 1989 Cook, William Oscar, II
Date Available in IDEALS:2011-05-07
Identifier in Online Catalog:AAI9010837
OCLC Identifier:(UMI)AAI9010837

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