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

ABSTRACT: 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.

SUBMITTER: Maruo VM

PROVIDER: S-EPMC5983239 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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

Maruo Viviane Mayumi VM Bracarense Ana Paula AP Metayer Jean-Paul JP Vilarino Maria M Oswald Isabelle P IP Pinton Philippe P

Toxins 20180501 5

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 ...[more]

PMID: 29723978

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Project description:Fescue toxicosis is a syndrome that impairs growth and reproduction in cattle grazing endophyte-infected tall fescue [Lolium arundinaceum [(Schreb.].) Darbysh)] in the United States, resulting in approximately $1 billion in annual economic loss in species that utilize this forage resource. Approximately 90% of tall fescue contains an endophytic fungus (Epichloë coenophiala) that produces ergot alkaloids. Ergot alkaloids cause vasoconstriction and reduced blood flow to the extremities; however, it remains unknown how blood flow to the reproductive organs is affected in cattle. Therefore, the objective of this study was to determine if ergot alkaloids from endophyte-infected tall fescue reduce blood flow to the reproductive organs, thus hindering reproductive function. Angus heifers (n = 36) naïve to ergot alkaloids were placed in Calan gates and randomly assigned to receive either endophyte-infected fescue seed (E+) or noninfected fescue seed (E-; control) in a total mixed ration for 63 d. Weekly measurements were taken to monitor heifer growth and response to ergot alkaloid exposure. Reproductive measurements, including ovarian structures, uterine and ovarian vessel diameter, and hormone concentrations were determined after heifers were synchronized using the standard CO-Synch + 7 d CIDR protocol to ensure all measurements were collected at the same stages of the estrous cycle (0, 4, 10, and 17 d). Data were analyzed using repeated measures in PROC MIXED of SAS. Average daily gain was decreased for the E+ group (0.8 kg/d) compared to control heifers (1.0 kg/d). Body condition scores tended to be greater in control heifers compared to the E+ group (P = 0.053). Additionally, hair coat and hair shedding scores were greater in E+ heifers compared to controls (P < 0.05). Heart rate, rectal temperature, respiration rate, and blood pressure did not differ between treatments (P > 0.05). Vasoconstriction was observed in the caudal artery, but not the caudal vein, in heifers consuming the E+ fescue seed (P < 0.05). No differences were observed in antral follicle counts, corpus luteum area or circulating progesterone concentrations in E+ heifers compared to controls (P > 0.05). There was a significant decrease in the diameter of arteries and veins servicing the ovary and uterus on day 10 and 17 of the estrous cycle. Reduction in blood flow to the reproductive organs during critical times in the estrous cycle may contribute to the reduced ovarian function and pregnancy rates associated with fescue toxicosis.

Dataset Information

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

Publications

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

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