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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MDPI AG
2018-05-01
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author | Viviane Mayumi Maruo Ana Paula Bracarense Jean-Paul Metayer Maria Vilarino Isabelle P. Oswald Philippe Pinton |
author_facet | Viviane Mayumi Maruo Ana Paula Bracarense Jean-Paul Metayer Maria Vilarino Isabelle P. Oswald Philippe Pinton |
author_sort | Viviane Mayumi Maruo |
collection | DOAJ |
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 | doaj.art-70c82d363a1e4ceabdb4165a2c28923d2022-12-22T04:01:49ZengMDPI AGToxins2072-66512018-05-0110518310.3390/toxins10050183toxins10050183Ergot Alkaloids at Doses Close to EU Regulatory Limits Induce Alterations of the Liver and IntestineViviane Mayumi Maruo0Ana Paula Bracarense1Jean-Paul Metayer2Maria Vilarino3Isabelle P. Oswald4Philippe Pinton5Universidade Federal do Tocantins, Araguaína 77824-838, BrazilLaboratory of Animal Pathology, Universidade Estadual de Londrina, Londrina 86057-970, BrazilARVALIS-Institut du Végétal, Station expérimentale, 41100 Villerable, FranceARVALIS-Institut du Végétal, Station expérimentale, 41100 Villerable, FranceToxalim (Research Centre in Food Toxicology), Université de Toulouse, INRA, ENVT, INP-Purpan, UPS, 31027 Toulouse, FranceToxalim (Research Centre in Food Toxicology), Université de Toulouse, INRA, ENVT, INP-Purpan, UPS, 31027 Toulouse, FranceAn 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.http://www.mdpi.com/2072-6651/10/5/183Clavicepsliverdigestive tractmycotoxinsclerotiaergot alkaloidstoxicity |
spellingShingle | Viviane Mayumi Maruo Ana Paula Bracarense Jean-Paul Metayer Maria Vilarino Isabelle P. Oswald Philippe Pinton Ergot Alkaloids at Doses Close to EU Regulatory Limits Induce Alterations of the Liver and Intestine Toxins Claviceps liver digestive tract mycotoxin sclerotia ergot alkaloids toxicity |
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 | Claviceps liver digestive tract mycotoxin sclerotia ergot alkaloids toxicity |
url | http://www.mdpi.com/2072-6651/10/5/183 |
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