Fumonisin B1 exposure induces cardiac inflammation in C57BL/6 mice

Abstract

The increasing prevalence of mycotoxin toxicity poses significant health risks, contributing to various diseases. Among these, fumonisin B1 (FB₁) alters sphingolipid biosynthesis, induces oxidative stress, apoptosis, mitochondrial dysfunction, and inflammation. This study investigated the impact of acute FB₁ exposure on inflammation and epigenetics changes in hearts of C57BL/6 mice. Molecular docking was performed to identify potential interactions between FB₁ and key inflammatory proteins (TNF-α, iNOS, NF-κB p65, and NF-κB p50). Excised C57BL/6 mice heart tissue was analysed for gene expression (qPCR), protein expression (Western blotting), nitric oxide levels (NOS assay), cytokine levels (ELISA), and global DNA methylation (ELISA). Molecular docking suggested FB₁ interacted with key residues in TNF-α, iNOS, and NF-κB, potentially influencing their activity. Gene expression analysis (TNF-α, NF-κB, IL-6, NLRP3 Inflammasome, IL-18, caspase 1, IL-1β, GSDMD, caspase 3, CT-1, IL-10, MBD2, DNMT1, DNMT3A, and DNMT3B) revealed that FB₁ significantly dysregulated inflammatory cytokines and DNA methylation-related genes. Protein expression analysis showed significant upregulation of pro-inflammatory cytokines (TNF-α, NF-κB, IL-6, IL-1β, IL-18, IL-10, and TGF-β1). Global DNA methylation levels were significantly increased, with notable upregulation of DNMT1. In conclusion, acute exposure of C57BL/6 mice to FB₁ significantly impacted inflammatory and DNA methylation pathways, leading to cardiac distress complications.