Nivalenol has a greater impact than deoxynivalenol on pig jejunum mucosa in vitro on explants and in vivo on intestinal loops.

Sophal Cheat,Isabelle Raymond-Letron,Martine Kolf-Clauw,Imourana Alassane-Kpembi,Ana Bracarense,Juliana Gerez,Juliette Cognié,Isabelle Oswald

doi:10.3390/toxins7061945

Abstract

The mycotoxins deoxynivalenol (DON) and nivalenol (NIV), worldwide cereal contaminants, raise concerns for animal and human gut health, following contaminated food or feed ingestion. The impact of DON and NIV on intestinal mucosa was investigated after acute exposure, in vitro and in vivo. The histological changes induced by DON and NIV were analyzed after four-hour exposure on pig jejunum explants and loops, two alternative models. On explants, dose-dependent increases in the histological changes were induced by DON and NIV, with a two-fold increase in lesion severity at 10 µM NIV. On loops, NIV had a greater impact on the mucosa than DON. The overall proliferative cells showed 30% and 13% decrease after NIV and DON exposure, respectively, and NIV increased the proliferative index of crypt enterocytes. NIV also increased apoptosis at the top of villi and reduced by almost half the proliferative/apoptotic cell ratio. Lamina propria cells (mainly immune cells) were more sensitive than enterocytes (epithelial cells) to apoptosis induced by NIV. Our results demonstrate a greater impact of NIV than DON on the intestinal mucosa, both in vitro and in vivo, and highlight the need of a specific hazard characterization for NIV risk assessment.

Highlights

Fungi of the Fusarium genus commonly contaminate cereals in the temperate climatic zones of the world and contribute to poor quality grains entering the feed and food chain
Two alternative models were used in this study to analyze intestinal mucosal toxicity, a major target for xenobiotics
The Jejunum Explants and Loops Alternative Models Reduce the Number of Animals. These two alternative models enabled to reduce the number of animals in experiments, according to the 3Rs recommendations, as the explants or loops are the experimental unit and not the whole animal

Summary

Introduction

Fungi of the Fusarium genus commonly contaminate cereals in the temperate climatic zones of the world and contribute to poor quality grains entering the feed and food chain. A large-scale data survey has indicated that DON and NIV are present in 57% and 16%, respectively, of food samples collected in the European Union [5] From their first discovery, there has been concern about the relationship between trichothecenes exposure and health damage based on both experimental toxicity and epidemiological data. DON and NIV, like other trichothecenes, display multiple inhibitory effects on the primary metabolism of eukaryotic cells including the inhibition of proteins, DNA and RNA synthesis [10] This impairment leads to altered cell proliferation in tissues with high rates of cell turnover such as spleen, bone marrow, thymus and intestinal mucosa [11]

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Results

Discussion

Conclusion