A model system for studying the bioavailability of intestinally administered microcystin-LR, a hepatotoxic peptide from the cyanobacterium Microcystis aeruginosa.
Sprague-Dawley rats were used to evaluate a model system for studying the hepatotoxicity caused by microcystin-LR (MCYST-LR), a toxin produced by the cyanobacterium (blue-green alga) Microcystis aeruginosa, and for evaluating the in vivo therapeutic potential of cholestyramine resin (CTR) which was found to bind the toxin in vitro. Female rats were treated with either toxin or an equivalent volume of the saline vehicle by direct administration into the lumen of an in situ isolated ileal loop. Male rats were dosed with toxin as described above, and then animals were dosed in the ileal loop with either cholestyramine resin (CTR, 50 mg/rat) or an equivalent vehicle. The survivors in both studies were killed six hours after dosing and hepatotoxicity was assessed by change in relative liver weights. In all groups given toxin alone, there was a significant increase in liver weight and males and females were equally susceptible. Liver weights of the toxin plus CTR treated rats were similar to those in vehicle-treated rats. When the toxin was administered into a similarly isolated jejunal loop, liver weight was significantly less than that found when an equivalent dose was administered into the ileal loop suggesting an intestinal site specificity for toxin absorption.
Dahlem
A M
AM
Department of Veterinary Biosciences, College of Veterinary Medicine, University of Illinois, Urbana 61801.
Hassan
A S
AS
Swanson
S P
SP
Carmichael
W W
WW
Beasley
V R
VR
D000818:Animals; D001682:Biological Availability; D056486:Chemical and Drug Induced Liver Injury; D002792:Cholestyramine Resin / Q000494:pharmacology; D005260:Female; D007082:Ileum; D007408:Intestinal Absorption; D007583:Jejunum; D008026:Ligation; D008107:Liver Diseases / Q000473:pathology; D008297:Male; D008387:Marine Toxins; D052998:Microcystins; D046931:Microcystis / Q000378:metabolism; D008954:Models, Biological; D010456:Peptides, Cyclic / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains; D014118:Toxins, Biological / Q000008:administration & dosage / Q000493:pharmacokinetics*
D008387:Marine Toxins; D052998:Microcystins; D010456:Peptides, Cyclic; D014118:Toxins, Biological; D002792:Cholestyramine Resin; C057862:cyanoginosin LR