Protective effect of a novel furan hybrid chalcone against bisphenol A-induced craniofacial developmental toxicity in zebrafish embryos

Bisphenol A (BPA), a pervasive endocrine disruptor, is known to cause significant developmental toxicity, particularly affecting craniofacial structures through oxidative stress and apoptosis. A novel furan hybrid chalcone derivative, 3-(2-hydroxy-5-nitrophenyl)-1-(5-methylfuran-2-yl)prop-2-en-1-one (DK04), specifically with a hydroxyl group for its antioxidant properties and a nitro group for enhanced electron-withdrawing ability, was evaluated for its potential to mitigate these toxic effects. Zebrafish embryos were exposed to BPA and co-treated with various concentrations of DK04. Our results demonstrated that DK04 significantly reduced reactive oxygen species (ROS) generation and lipid peroxidation, increased antioxidant enzyme activities (SOD and CAT), and restored the balance between pro-apoptotic (p53) and anti-apoptotic (bcl2) genes. Furthermore, DK04 treatment improved bone mineralization and chondrogenesis by reversing BPA-induced disruptions in osteogenic markers (runx2, sox9a, bmp6, and mmp13a). The locomotion impairments observed in BPA-exposed embryos were also ameliorated by DK04, indicating its potential neuroprotective effects. These findings suggest that DK04 offers a multifaceted approach to counteract BPA toxicity, making it a promising candidate for therapeutic intervention. This research underscores the importance of developing prophylactic compounds to safeguard health against environmental toxicants like BPA. Future studies should focus on long-term safety and efficacy in mammalian models and explore synergistic effects with other protective agents to broaden the applications of DK04 and contribute to public health benefits.