Inflammatory activation and MAPK signaling mediate fumonisin B1-induced myocardial dysfunction

Fumonisin B1 (FB1) poses serious health concerns to human health. In this research, the cardiotoxic effects of FB1 were comprehensively evaluated through in vitro experiments using H9C2 cardiomyocytes and in vivo assays utilizing zebrafish. In H9C2 cells, exposure to 40 mg/L FB1 resulted in marked mitochondrial damage and apoptotic cell death. Transcriptomic profiling identified 1292 differentially expressed genes, with significant enrichment in pro-inflammatory signaling pathways, containing TNF, NOD-like receptor, and MAPK pathways. These findings were corroborated by the elevated expression of inflammatory mediators, i.e., IL-6, IL-8, and NF-κB, along with elevated phosphorylation of NF-κB p65 and MAPK ERK proteins, indicating the activation of these signaling cascades. In zebrafish, FB1 (40 mg/L) induced pronounced oxidative stress, cardiac malformations, functional disruptions, and heightened inflammatory responses. These molecular and functional disturbances ultimately resulted in compromised cardiac gene expression and physiological impairment, offering novel mechanistic insights into FB1-induced cardiovascular toxicity and underscoring its potential risk to cardiac health.