Enniatin B attenuates deoxynivalenol-induced toxicity in liver cells and modulates lipid metabolism-related pathways.

Authors

Denis Habauzit, Sylvie Huet, Emeline Nicolas, Patrick Balaguer, Thibaut Léger

Published in

Environment international. Volume 215. Pages 110498. Sep 02, 2026. Epub Sep 02, 2026.

Abstract

Mycotoxin contamination of food and feed is an increasing global health concern, particularly due to Fusarium toxins such as the regulated deoxynivalenol (DON) and the emerging enniatin B (ENNB). However, the combined mechanisms of action of these toxins remain poorly understood. This study aimed to assess their toxic effects, alone and in combination, using the HepaRG liver cell model. Toxicity, individually and in combination at concentrations equivalent to those used in single exposures (5:1 DON to ENNB ratio), was assessed in HepaRG cells. Several endpoints were investigated, including viability (cell number), γH2AX formation and apoptosis (active caspase-3) by High Content Analysis (HCA) as well as the pro-inflammatory response (IL-8 sretion) by ELISA. DON induced a concentration-dependent decrease in cell number and increased the levels of active caspase-3, γH2AX and IL-8. In contrast, ENNB only slightly reduced cell viability. Interestingly, the combination limited DON-induced cell death, DNA damage and apoptosis. To further investigate which pathways are involved in toxicity, proteomics and metabolomics analyses were performed. DON increased long-chain saturated dicarboxylic acids, suggesting impaired fatty acid oxidation (FAO), histones and proteins related to mitochondrial respiration while reducing FAO-related proteins. These effects were mitigated by ENNB, suggesting opposite effects of the toxins. This mitigation appeared to be consistentwith the involvement of peroxisome proliferator-activated receptor alpha (PPARα) signaling, though without direct receptor activation by either substance. We present insights into DON and ENNB toxicity and highlight the importance of considering combined effects in risk assessment.

PMID:
42700669
Bibliographic data and abstract were imported from PubMed on 06 Sep 2026.

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