Document Detail

Metabolomic analyses of body fluids after subchronic manganese inhalation in rhesus monkeys.
MedLine Citation:
PMID:  18684773     Owner:  NLM     Status:  MEDLINE    
Neurotoxicity is linked with high-dose manganese inhalation. There are few biomarkers that correlate with manganese exposure. Blood manganese concentrations depend upon the magnitude and duration of the manganese exposure and inconsistently reflect manganese exposure concentrations. The objective of this study was to search for novel biomarkers of manganese exposure in the urine and blood obtained from rhesus monkeys following subchronic manganese sulfate (MnSO(4)) inhalation. Liquid chromatography-mass spectrometry was used to identify putative biomarkers. Juvenile rhesus monkeys were exposed 5 days/week to airborne MnSO(4) at 0, 0.06, 0.3, or 1.5 mg Mn/m(3) for 65 exposure days or 1.5 mg Mn/m(3) for 15 or 33 days. Monkeys exposed to MnSO(4) at >or= 0.06 mg Mn/m(3) developed increased brain manganese concentrations. A total of 1097 parent peaks were identified in whole blood and 2462 peaks in urine. Principal component analysis was performed on a subset of 113 peaks that were found to be significantly changed following subchronic manganese exposure. Using the Nearest Centroid analysis, the subset of 113 significantly perturbed components predicted globus pallidus manganese concentrations with 72.9% accuracy for all subchronically exposed monkeys. Using the five confirmed components, the prediction rate for high brain manganese levels remained > 70%. Three of the five identified components, guanosine, disaccharides, and phenylpyruvate, were significantly correlated with brain manganese levels. In all, 27 metabolites with statistically significant expression differences were structurally confirmed by MS-MS methods. Biochemical changes identified in manganese-exposed monkeys included endpoints relate to oxidative stress (e.g., oxidized glutathione) and neurotransmission (aminobutyrate, glutamine, phenylalanine).
David C Dorman; Melanie F Struve; Amy Norris; Alan J Higgins
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2008-08-06
Journal Detail:
Title:  Toxicological sciences : an official journal of the Society of Toxicology     Volume:  106     ISSN:  1096-0929     ISO Abbreviation:  Toxicol. Sci.     Publication Date:  2008 Nov 
Date Detail:
Created Date:  2008-10-09     Completed Date:  2008-12-23     Revised Date:  2010-09-17    
Medline Journal Info:
Nlm Unique ID:  9805461     Medline TA:  Toxicol Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  46-54     Citation Subset:  IM    
College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina 27606-1499, USA.
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MeSH Terms
Air Pollutants / blood,  toxicity*,  urine
Biological Markers* / blood,  urine
Chromatography, Liquid
Cluster Analysis
Environmental Monitoring*
Globus Pallidus / drug effects*,  metabolism
Inhalation Exposure
Macaca mulatta
Manganese Compounds / blood,  urine
Metabolomics* / methods
Principal Component Analysis
Sulfates / blood,  toxicity*,  urine
Tandem Mass Spectrometry
Reg. No./Substance:
0/Air Pollutants; 0/Biological Markers; 0/Manganese Compounds; 0/Sulfates; 7785-87-7/manganese sulfate

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