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Ergot Alkaloids at Doses Close to EU Regulatory Limits Induce Alterations of the Liver and Intestine

An increase in the occurrence of ergot alkaloids (EAs) contamination has been observed in North America and Europe in recent years. These toxins are well known for their effects on the circulatory and nervous systems. The aim of this study was to investigate the effect of EAs on the liver and on the...

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Autores principales: Maruo, Viviane Mayumi, Bracarense, Ana Paula, Metayer, Jean-Paul, Vilarino, Maria, Oswald, Isabelle P., Pinton, Philippe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5983239/
https://www.ncbi.nlm.nih.gov/pubmed/29723978
http://dx.doi.org/10.3390/toxins10050183
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author Maruo, Viviane Mayumi
Bracarense, Ana Paula
Metayer, Jean-Paul
Vilarino, Maria
Oswald, Isabelle P.
Pinton, Philippe
author_facet Maruo, Viviane Mayumi
Bracarense, Ana Paula
Metayer, Jean-Paul
Vilarino, Maria
Oswald, Isabelle P.
Pinton, Philippe
author_sort Maruo, Viviane Mayumi
collection PubMed
description An increase in the occurrence of ergot alkaloids (EAs) contamination has been observed in North America and Europe in recent years. These toxins are well known for their effects on the circulatory and nervous systems. The aim of this study was to investigate the effect of EAs on the liver and on the intestine using the pig both as a target species and as a non-rodent model for human. Three groups of 24 weaned piglets were exposed for 28 days to control feed or feed contaminated with 1.2 or 2.5 g of sclerotia/kg, i.e., at doses close to EU regulatory limits. Contaminated diets significantly reduced feed intake and consequently growth performance. In the liver, alteration of the tissue, including development of inflammatory infiltrates, vacuolization, apoptosis and necrosis of hepatocytes as well as presence of enlarged hepatocytes (megalocytes) were observed. In the jejunum, EAs reduced villi height and increased damage to the epithelium, reduced the number of mucus-producing cells and upregulated mRNA coding for different tight junction proteins such as claudins 3 and 4. In conclusion, in term of animal health, our data indicate that feed contaminated at the regulatory limits induces lesions in liver and intestine suggesting that this limit should be lowered for pigs. In term of human health, we establish a lowest observed adverse effect level (LOAEL) of 100 μg/kg body weight (bw) per day, lower than the benchmark dose limit (BMDL) retained by European Food Safety Authority (EFSA) to set the tolerable daily intake, suggesting also that regulatory limit should be revised.
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spelling pubmed-59832392018-06-06 Ergot Alkaloids at Doses Close to EU Regulatory Limits Induce Alterations of the Liver and Intestine Maruo, Viviane Mayumi Bracarense, Ana Paula Metayer, Jean-Paul Vilarino, Maria Oswald, Isabelle P. Pinton, Philippe Toxins (Basel) Article An increase in the occurrence of ergot alkaloids (EAs) contamination has been observed in North America and Europe in recent years. These toxins are well known for their effects on the circulatory and nervous systems. The aim of this study was to investigate the effect of EAs on the liver and on the intestine using the pig both as a target species and as a non-rodent model for human. Three groups of 24 weaned piglets were exposed for 28 days to control feed or feed contaminated with 1.2 or 2.5 g of sclerotia/kg, i.e., at doses close to EU regulatory limits. Contaminated diets significantly reduced feed intake and consequently growth performance. In the liver, alteration of the tissue, including development of inflammatory infiltrates, vacuolization, apoptosis and necrosis of hepatocytes as well as presence of enlarged hepatocytes (megalocytes) were observed. In the jejunum, EAs reduced villi height and increased damage to the epithelium, reduced the number of mucus-producing cells and upregulated mRNA coding for different tight junction proteins such as claudins 3 and 4. In conclusion, in term of animal health, our data indicate that feed contaminated at the regulatory limits induces lesions in liver and intestine suggesting that this limit should be lowered for pigs. In term of human health, we establish a lowest observed adverse effect level (LOAEL) of 100 μg/kg body weight (bw) per day, lower than the benchmark dose limit (BMDL) retained by European Food Safety Authority (EFSA) to set the tolerable daily intake, suggesting also that regulatory limit should be revised. MDPI 2018-05-01 /pmc/articles/PMC5983239/ /pubmed/29723978 http://dx.doi.org/10.3390/toxins10050183 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Maruo, Viviane Mayumi
Bracarense, Ana Paula
Metayer, Jean-Paul
Vilarino, Maria
Oswald, Isabelle P.
Pinton, Philippe
Ergot Alkaloids at Doses Close to EU Regulatory Limits Induce Alterations of the Liver and Intestine
title Ergot Alkaloids at Doses Close to EU Regulatory Limits Induce Alterations of the Liver and Intestine
title_full Ergot Alkaloids at Doses Close to EU Regulatory Limits Induce Alterations of the Liver and Intestine
title_fullStr Ergot Alkaloids at Doses Close to EU Regulatory Limits Induce Alterations of the Liver and Intestine
title_full_unstemmed Ergot Alkaloids at Doses Close to EU Regulatory Limits Induce Alterations of the Liver and Intestine
title_short Ergot Alkaloids at Doses Close to EU Regulatory Limits Induce Alterations of the Liver and Intestine
title_sort ergot alkaloids at doses close to eu regulatory limits induce alterations of the liver and intestine
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5983239/
https://www.ncbi.nlm.nih.gov/pubmed/29723978
http://dx.doi.org/10.3390/toxins10050183
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