Document Detail


Gene expression of biomarkers of nephrotoxicity in F344 rats co-exposed to melamine and cyanuric acid for seven days.
MedLine Citation:
PMID:  21784140     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A number of studies have demonstrated that co-exposure to low levels of melamine and cyanuric acid elicits renal toxicity due to the formation of melamine cyanurate crystals in the kidney nephrons. In this work, we investigated if co-exposure of rats to these compounds leads to alterations in the expression of the genes encoding kidney injury molecule 1 (KIM-1), metallopeptidase inhibitor 1 (TIMP1), clusterin, osteopontin, and neutrophil gelatinase-associated lipocalin/lipocalin 2 (NGAL), which have been proposed as urinary biomarkers for nephrotoxicity. Six-week-old male and female F344 rats were fed ad libitum a diet fortified with 0 (control), 7, 23, 69, 229, or 694 ppm melamine and cyanuric acid (co-exposure groups), 1388 ppm melamine, or 1388 ppm cyanuric acid for seven days. Histopathology and clinical chemistry examination indicated marked toxicity only in the animals exposed to the two highest combined doses of melamine and cyanuric acid. Consistent with these observations, quantitative real-time polymerase chain reaction analysis of kidney tissue indicated increased expression of all genes analyzed relative to the control in both male and female rats fed daily with 229 or 694 ppm melamine and cyanuric acid. Exposure to lower levels of both compounds or to the individual compounds did not induce gene expression changes. These data indicate that quantifying the expression levels of the selected biomarker genes constitutes a useful endpoint to assess the combined toxicity of melamine and cyanuric acid in both male and female rats.
Authors:
Luísa Camacho; Kevin P Kelly; Frederick A Beland; Gonçalo Gamboa da Costa
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2011-07-18
Journal Detail:
Title:  Toxicology letters     Volume:  206     ISSN:  1879-3169     ISO Abbreviation:  Toxicol. Lett.     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-08-29     Completed Date:  2011-10-21     Revised Date:  2013-06-28    
Medline Journal Info:
Nlm Unique ID:  7709027     Medline TA:  Toxicol Lett     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  166-71     Citation Subset:  IM    
Copyright Information:
Published by Elsevier Ireland Ltd.
Affiliation:
Division of Biochemical Toxicology, National Center for Toxicological Research, 3900 NCTR Road, Jefferson, AR 72079, USA. luisa.camacho@fda.hhs.gov
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MeSH Terms
Descriptor/Qualifier:
Acute-Phase Proteins / genetics,  metabolism
Animals
Biological Markers / metabolism
Cell Adhesion Molecules / genetics,  metabolism
Clusterin / genetics,  metabolism
Dose-Response Relationship, Drug
Environmental Pollutants / administration & dosage,  toxicity*
Female
Gene Expression Regulation / drug effects*
Kidney / drug effects*,  metabolism*
Lipocalins / genetics,  metabolism
Male
No-Observed-Adverse-Effect Level
Osteopontin / genetics,  metabolism
Proto-Oncogene Proteins / genetics,  metabolism
RNA, Messenger / metabolism
Rats
Rats, Inbred F344
Renal Insufficiency / chemically induced*,  metabolism
Sex Characteristics
Tissue Inhibitor of Metalloproteinase-1 / genetics,  metabolism
Triazines / administration & dosage,  toxicity*
Grant Support
ID/Acronym/Agency:
Y01 ES001027-35/ES/NIEHS NIH HHS; Y1ES1027/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
0/Acute-Phase Proteins; 0/Biological Markers; 0/Cell Adhesion Molecules; 0/Clu protein, rat; 0/Clusterin; 0/Environmental Pollutants; 0/Havcr1protein, rat; 0/Lcn2 protein, rat; 0/Lipocalins; 0/Proto-Oncogene Proteins; 0/RNA, Messenger; 0/Spp1 protein, rat; 0/Tissue Inhibitor of Metalloproteinase-1; 0/Triazines; 0/neutrophil gelatinase-associated lipocalin protein, rat; 106441-73-0/Osteopontin; H497R4QKTZ/cyanuric acid; N3GP2YSD88/melamine
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