Neuroprotective effects of ferulic acid and thymoquinone against deltamethrin-induced neurotoxicity in Drosophila melanogaster

B ackground: Recent research indicates a link between exposure to pyrethroid pesticides and negative neurodevelopmental outcomes such as neurodegenerative disorders, low intelligence quotient (IQ), and attention disorders. Thus this study aims (1) to investigate the effect of exposing Drosophila melanogaster adult male flies to 0.59 µM deltamethrin (DLM) for 24 h on their survival, climbing behavior, and acetylcholinesterase (AChE) activity, as well as the gene expression levels of ple, ddc, dat, aanat1, dop1r1, dop2r, and dopecr genes, and (2) to assess the protective effect of 250 µM Ferulic acid (FA), 25 µM Thymoquinone (TQ), and their combinations on the survival, climbing behavior, and AChE activity of D. melanogaster adult male flies exposed to 0.59 µM DLM for 72 h. Methods: In the first experiment, adult male wild-type flies were exposed to DLM incorporated into a 10% sucrose solution for 24 h, whereas, in the second experiment, they were exposed to DLM and the individual neuroprotective agents, or their mixture for 72 h. Results: Flies exposed to DLM exhibited higher mortality rates and shorter climbing distances in the negative geotaxis assay compared to control flies. Additionally, exposure to DLM upregulated the genes ddc, dat, dop1r1, dop2r, and dopecr significantly. Moreover, exposure to DLM for 72 h resulted in higher mortality rates and severe locomotor defects. However, the neuroprotective agents were effective in mitigating these toxic effects. While DLM inhibited AChE activity, concurrent exposure to FA ameliorated the inhibition. Conclusion: This study demonstrates the efficacy of natural compounds in reducing DLM-induced toxicity in D. melanogaster and highlights the potential use of this model in studying and developing therapeutic strategies for movement disorders.