NDLI: Integrated histopathological and urinary metabonomic investigation of the pathogenesis of microcystin-LR toxicosis.

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Integrated histopathological and urinary metabonomic investigation of the pathogenesis of microcystin-LR toxicosis.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Cantor, G. H. Beckonert, O. Bollard, M. E. Keun, H. C. Ebbels, T. M. D. Antti, H. Wijsman, J. A. Bible, R. H. Breau, A. P. Cockerell, G. L. Holmes, E. Lindon, J. C. Nicholson, J. K.
Description	Country affiliation: United States Author Affiliation: Cantor GH ( Discovery Toxicology, Bristol-Myers Squibb Co, Princeton, NJ 08543, USA. glenn.cantor@bms.com)
Abstract	Patterns of change of endogenous metabolites may closely reflect systemic and organ-specific toxic changes. The authors examined the metabolic effects of the cyanobacterial (blue-green algal) toxin microcystin-LR by (1)H-nuclear magnetic resonance (NMR) analysis of urinary endogenous metabolites. Rats were treated with a single sublethal dose, either 20 or 80 µg/kg intraperitoneally, and sacrificed at 2 or 7 days post dosing. Changes in the high-dose, 2-day sacrifice group included centrilobular hepatic necrosis and congestion, accompanied in some animals by regeneration and neovascularization. By 7 days, animals had recovered, the necrotizing process had ended, and the centrilobular areas had been replaced by regenerative, usually hypertrophic hepatocytes. There was considerable interanimal variation in the histologic process and severity, which correlated with the changes in patterns of endogenous metabolites in the urine, thus providing additional validation of the biomarker and biochemical changes. Similarity of the shape of the metabolic trajectories suggests that the mechanisms of toxic effects and recovery are similar among the individual animals, albeit that the magnitude and timing are different for the individual animals. Initial decreases in urinary citrate, 2-oxoglutarate, succinate, and hippurate concentrations were accompanied by a temporary increase in betaine and taurine, then creatine from 24 to 48 hours. Further changes were an increase in guanidinoacetate, dimethylglycine, urocanic acid, and bile acids. As a tool, urine can be repeatedly and noninvasively sampled and metabonomics utilized to study the onset and recovery after toxicity, thus identifying time points of maximal effect. This can help to employ histopathological examination in a guided and effective fashion.
File Format	HTM / HTML
ISSN	03009858
Issue Number	1
Volume Number	50
e-ISSN	15442217
Journal	Veterinary Pathology
Language	English
Publisher	Sage Publication
Publisher Date	2013-01-01
Publisher Place	United States
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Discipline Veterinary Medicine Discipline Pathology Enzyme Inhibitors Toxicity Kidney Drug Effects Liver Metabolomics Methods Microcystins Microcystis Chemistry Animals Bile Acids And Salts Urine Metabolism Injections, Intraperitoneal Pathology Magnetic Resonance Spectroscopy Male Rats Rats, Sprague-dawley Time Factors Urocanic Acid Journal Article Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Veterinary

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