Dual In Vivo and In Silico Exploration of Jet A-1 Fuel Toxicity

Abstract

Occupational and environmental exposure to aviation fuel requires rigorous toxicity evaluation to protect public health. This study assessed the neurotoxic potential of Jet A-1 aviation fuel using a combined in vivo and in silico approach. In Drosophila melanogaster, continuous exposure to Jet A-1 significantly reduced survival and locomotor activity in both sexes. RT-qPCR analysis revealed increased expression of AChE, rpr, sod1, sod2, and cat, indicating cholinergic dysfunction, activation of the apoptotic pathway, and increased oxidative stress. Given the high naphthalene content in Jet A-1 fuel, network pharmacology analysis identified approximately 129 complementary targets associated with naphthalene derivative-induced neurotoxicity. These targets were enriched in pathways related to apoptosis, oxidative stress, impaired proteostasis, and inflammatory signaling, suggesting a multifactorial neurotoxic response. Further molecular docking analysis demonstrated strong interactions between Jet-A1 and key proteins such as AKT1, EGFR, PTEN, CSK, SHG, and Decay, corroborating the in vivo findings. Together, these results elucidate the mechanistic basis of Jet A-1-induced neurotoxicity and reinforce the value of D. melanogaster as a reliable in vivo model for high-throughput toxicological studies of chemical exposure.