| Gene expression of biomarkers of nephrotoxicity in F344 rats co-exposed to melamine and cyanuric acid for seven days. | |
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MedLine Citation:
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PMID: 21784140 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Luísa Camacho; Kevin P Kelly; Frederick A Beland; Gonçalo Gamboa da Costa |
Publication Detail:
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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:
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Title: Toxicology letters Volume: 206 ISSN: 1879-3169 ISO Abbreviation: Toxicol. Lett. Publication Date: 2011 Oct |
Date Detail:
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Created Date: 2011-08-29 Completed Date: 2011-10-21 Revised Date: 2011-10-21 |
Medline Journal Info:
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Nlm Unique ID: 7709027 Medline TA: Toxicol Lett Country: Netherlands |
Other Details:
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Languages: eng Pagination: 166-71 Citation Subset: IM |
Copyright Information:
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Published by Elsevier Ireland Ltd. |
Affiliation:
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Division of Biochemical Toxicology, National Center for Toxicological Research, 3900 NCTR Road, Jefferson, AR 72079, USA. luisa.camacho@fda.hhs.gov |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Acute-Phase Proteins
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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:
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Y1ES1027/ES/NIEHS NIH HHS |
| Chemical | |
Reg. No./Substance:
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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; 108-78-1/melamine; 108-80-5/cyanuric acid |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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