# Nivalenol Has a Greater Impact than Deoxynivalenol on Pig Jejunum Mucosa in Vitro on Explants and in Vivo on Intestinal Loops

**Authors:** Sophal Cheat, Juliana R. Gerez, Juliette Cognié, Imourana Alassane-Kpembi, Ana Paula F. L. Bracarense, Isabelle Raymond-Letron, Isabelle P. Oswald, Martine Kolf-Clauw

PMC · DOI: 10.3390/toxins7061945 · 2015-05-29

## TL;DR

Nivalenol causes more damage to pig intestines than deoxynivalenol, both in lab and live models, suggesting it poses a greater health risk.

## Contribution

This study is the first to compare the effects of NIV and DON on pig intestinal mucosa using both in vitro and in vivo models.

## Key findings

- Nivalenol caused twice as much mucosal damage as deoxynivalenol at 10 µM in pig jejunum explants.
- Nivalenol reduced proliferative cells by 30% and increased apoptosis in intestinal villi more than deoxynivalenol.
- Lamina propria cells were more sensitive to Nivalenol-induced apoptosis than enterocytes.

## 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.

## Linked entities

- **Chemicals:** deoxynivalenol (PubChem CID 40024), nivalenol (PubChem CID 5284433)

## Full-text entities

- **Genes:** Peroxidase [NCBI Gene 108854338], caspase-3 [NCBI Gene 100034083]
- **Diseases:** Toxic (MESH:D064420), gastroenteritis (MESH:D005759), atrophy (MESH:D001284), Mucosa (MESH:D018442), gastrointestinal erosions (MESH:D005767), diarrhea (MESH:D003967), hemorrhage (MESH:D006470), Jejunum Mucosa (MESH:D007580), weight gain (MESH:D015430), endotoxemia (MESH:D019446), blood extravasation (MESH:D006402), mucosal toxicity (MESH:D052016), Edema of the (MESH:D004487), vomiting (MESH:D014839), vascular disorders (MESH:D002561), shock (MESH:D012769), anorexia (MESH:D000855), inflammatory (MESH:D007249), intestinal damage (MESH:D007410)
- **Chemicals:** acetone (MESH:D000096), DMSO (MESH:D004121), 3,3'-diaminobenzidine tetrahydrochloride (-), formalin (MESH:D005557), water (MESH:D014867), pentobarbital (MESH:D010424), eosin (MESH:D004801), lipid (MESH:D008055), hematoxylin (MESH:D006416), CO2 (MESH:D002245), DON (MESH:C007262), barbiturate (MESH:C032232), toluene (MESH:D014050), citrate (MESH:D019343), NIV (MESH:C038405), trichothecenes (MESH:D014255), trichothecene (MESH:C000630165), Paraffin (MESH:D010232)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Sus scrofa (pig, species) [taxon 9823], Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** IPEC-J2 — Sus scrofa (Pig), Spontaneously immortalized cell line (CVCL_2246), C57BL/6 — Mus musculus (Mouse), Transformed cell line (CVCL_C0MU), Caco-2 — Homo sapiens (Human), Colon adenocarcinoma, Cancer cell line (CVCL_0025), IEC-6 — Rattus norvegicus (Rat), Finite cell line (CVCL_0343), HepG2 — Homo sapiens (Human), Hepatoblastoma, Cancer cell line (CVCL_0027)

## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC4488683/full.md

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Source: https://tomesphere.com/paper/PMC4488683