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Cytotoxic Effects of Major and Emerging Mycotoxins on HepaRG Cells and Transcriptomic Response after Exposure of Spheroids to Enniatins B and B1.
Coulet, France; Coton, Monika; Iperi, Cristian; Belinger Podevin, Marine; Coton, Emmanuel; Hymery, Nolwenn.
Affiliation
  • Coulet F; Univ. Brest, INRAE, Laboratoire Universitaire de Biodiversité et Ecologie Microbienne, F-29280 Plouzané, France.
  • Coton M; Univ. Brest, INRAE, Laboratoire Universitaire de Biodiversité et Ecologie Microbienne, F-29280 Plouzané, France.
  • Iperi C; Autoimmunité et Immunothérapies UMR 51227, Inserm, University Brest, Lymphocytes B, F-29200 Brest, France.
  • Belinger Podevin M; Univ. Brest, INRAE, Laboratoire Universitaire de Biodiversité et Ecologie Microbienne, F-29280 Plouzané, France.
  • Coton E; Univ. Brest, INRAE, Laboratoire Universitaire de Biodiversité et Ecologie Microbienne, F-29280 Plouzané, France.
  • Hymery N; Univ. Brest, INRAE, Laboratoire Universitaire de Biodiversité et Ecologie Microbienne, F-29280 Plouzané, France.
Toxins (Basel) ; 16(1)2024 01 18.
Article in En | MEDLINE | ID: mdl-38251270
ABSTRACT
Mycotoxins, produced by fungi, frequently occur at different stages in the food supply chain between pre- and postharvest. Globally produced cereal crops are known to be highly susceptible to contamination, thus constituting a major public health concern. Among the encountered mycotoxigenic fungi in cereals, Fusarium spp. are the most frequent and produce both regulated (i.e., T-2 toxin, deoxynivalenol -DON-, zearalenone -ZEA-) and emerging (i.e., enniatins -ENNs-, beauvericin -BEA-) mycotoxins. In this study, we investigated the in vitro cytotoxic effects of regulated and emerging fusariotoxins on HepaRG cells in 2D and 3D models using undifferentiated and differentiated cells. We also studied the impact of ENN B1 and ENN B exposure on gene expression of HepaRG spheroids. Gene expression profiling pinpointed the differentially expressed genes (DEGs) and overall similar pathways were involved in responses to mycotoxin exposure. Complement cascades, metabolism, steroid hormones, bile secretion, and cholesterol pathways were all negatively impacted by both ENNs. For cholesterol biosynthesis, 23/27 genes were significantly down-regulated and could be correlated to a 30% reduction in cholesterol levels. Our results show the impact of ENNs on the cholesterol biosynthesis pathway for the first time. This finding suggests a potential negative effect on human health due to the essential role this pathway plays.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Depsipeptides / Mycotoxins / Antineoplastic Agents Type of study: Prognostic_studies Limits: Humans Language: En Journal: Toxins (Basel) Year: 2024 Document type: Article Affiliation country: Francia Country of publication: Suiza

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Depsipeptides / Mycotoxins / Antineoplastic Agents Type of study: Prognostic_studies Limits: Humans Language: En Journal: Toxins (Basel) Year: 2024 Document type: Article Affiliation country: Francia Country of publication: Suiza