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Inhibition of Heme Peroxidases by Melamine

In 2008 melamine-contaminated infant formula and dairy products in China led to over 50,000 hospitalizations of children due to renal injuries. In North America during 2007 and in Asia during 2004, melamine-contaminated pet food products resulted in numerous pet deaths due to renal failure. Animal s...

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Autores principales: Vanachayangkul, Pattaraporn, Tolleson, William H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3407616/
https://www.ncbi.nlm.nih.gov/pubmed/22852071
http://dx.doi.org/10.1155/2012/416062
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author Vanachayangkul, Pattaraporn
Tolleson, William H.
author_facet Vanachayangkul, Pattaraporn
Tolleson, William H.
author_sort Vanachayangkul, Pattaraporn
collection PubMed
description In 2008 melamine-contaminated infant formula and dairy products in China led to over 50,000 hospitalizations of children due to renal injuries. In North America during 2007 and in Asia during 2004, melamine-contaminated pet food products resulted in numerous pet deaths due to renal failure. Animal studies have confirmed the potent renal toxicity of melamine combined with cyanuric acid. We showed previously that the solubility of melamine cyanurate is low at physiologic pH and ionic strength, provoking us to speculate how toxic levels of these compounds could be transported through the circulation without crystallizing until passing into the renal filtrate. We hypothesized that melamine might be sequestered by heme proteins, which could interfere with heme enzyme activity. Four heme peroxidase enzymes were selected for study: horseradish peroxidase (HRP), lactoperoxidase (LPO), and cyclooxygenase-1 and -2 (COX-1 and -2). Melamine exhibited noncompetitive inhibition of HRP (K (i)  9.5 ± 0.7 mM), and LPO showed a mixed model of inhibition (K (i)  14.5 ± 4.7 mM). The inhibition of HRP and LPO was confirmed using a chemiluminescent peroxidase assay. Melamine also exhibited COX-1 inhibition, but inhibition of COX-2 was not detected. Thus, our results demonstrate that melamine inhibits the activity of three heme peroxidases.
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spelling pubmed-34076162012-07-31 Inhibition of Heme Peroxidases by Melamine Vanachayangkul, Pattaraporn Tolleson, William H. Enzyme Res Research Article In 2008 melamine-contaminated infant formula and dairy products in China led to over 50,000 hospitalizations of children due to renal injuries. In North America during 2007 and in Asia during 2004, melamine-contaminated pet food products resulted in numerous pet deaths due to renal failure. Animal studies have confirmed the potent renal toxicity of melamine combined with cyanuric acid. We showed previously that the solubility of melamine cyanurate is low at physiologic pH and ionic strength, provoking us to speculate how toxic levels of these compounds could be transported through the circulation without crystallizing until passing into the renal filtrate. We hypothesized that melamine might be sequestered by heme proteins, which could interfere with heme enzyme activity. Four heme peroxidase enzymes were selected for study: horseradish peroxidase (HRP), lactoperoxidase (LPO), and cyclooxygenase-1 and -2 (COX-1 and -2). Melamine exhibited noncompetitive inhibition of HRP (K (i)  9.5 ± 0.7 mM), and LPO showed a mixed model of inhibition (K (i)  14.5 ± 4.7 mM). The inhibition of HRP and LPO was confirmed using a chemiluminescent peroxidase assay. Melamine also exhibited COX-1 inhibition, but inhibition of COX-2 was not detected. Thus, our results demonstrate that melamine inhibits the activity of three heme peroxidases. Hindawi Publishing Corporation 2012 2012-07-18 /pmc/articles/PMC3407616/ /pubmed/22852071 http://dx.doi.org/10.1155/2012/416062 Text en Copyright © 2012 P. Vanachayangkul and W. H. Tolleson. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Vanachayangkul, Pattaraporn
Tolleson, William H.
Inhibition of Heme Peroxidases by Melamine
title Inhibition of Heme Peroxidases by Melamine
title_full Inhibition of Heme Peroxidases by Melamine
title_fullStr Inhibition of Heme Peroxidases by Melamine
title_full_unstemmed Inhibition of Heme Peroxidases by Melamine
title_short Inhibition of Heme Peroxidases by Melamine
title_sort inhibition of heme peroxidases by melamine
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3407616/
https://www.ncbi.nlm.nih.gov/pubmed/22852071
http://dx.doi.org/10.1155/2012/416062
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