Ergot alkaloids at doses close to EU regulatory limits induce alterations of the liver and intestine

Viviane Mayumi Maruo (1, 2) , Ana-Paula Loureiro-Bracarense (3) , Jean-Paul Metayer (4) , Maria Vilariño (4) , Isabelle P. Oswald (5) , Philippe Pinton (5)

1 ToxAlim - ToxAlim
2 UFT - Universidade Federal do Tocantins
3 Laboratory of Animal Pathology
4 ARVALIS - Institut du végétal [Paris]
5 ToxAlim-BioToMyc - Biosynthèse & Toxicité des Mycotoxines

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 g/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.

Mots clés: Claviceps; liver; digestive tract; mycotoxin; sclerotia; ergot alkaloids; toxicity

Domaines: Sciences du Vivant [q-bio]

Viviane Mayumi Maruo, Ana-Paula Loureiro-Bracarense, Jean-Paul Metayer, Maria Vilariño, Isabelle P. Oswald, et al.. Ergot alkaloids at doses close to EU regulatory limits induce alterations of the liver and intestine. Toxins, 2018, 10 (5), ⟨10.3390/toxins10050183⟩. ⟨hal-02625989⟩