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Validamycin A, an inhibitor of trehalase, possesses antibiotic and antifungal attributes. Epidemiological evidence has led to concerns regarding a potential link between pesticide usage and neurodegenerative diseases. The fruit fly, <jats:styled-content style=\"fixed-case\"><jats:italic>Drosophila melanogaster<\/jats:italic><\/jats:styled-content>, has been recognized as a reliable model for genetic research due to its significant genetic similarities with mammals. Here, we propose to use <jats:styled-content style=\"fixed-case\"><jats:italic>D.\u00a0melanogaster<\/jats:italic><\/jats:styled-content> as an effective in vivo model system to investigate the genotoxic risks associated with exposure to validamycin A. In this study, we performed a neurotoxic evaluation of validamycin A in <jats:styled-content style=\"fixed-case\"><jats:italic>D.\u00a0melanogaster<\/jats:italic><\/jats:styled-content> larvae. Several endpoints were evaluated, including toxicity, intracellular oxidative stress (reactive oxygen species), intestinal damage, larval behavior (crawling behavior, light\/dark sensitivity assay, and temperature sensitivity assay), locomotor (climbing) behavior, and neurogenotoxic effects (impaired DNA via Comet assay, enhanced by Endo III and formamidopyrimidine DNA glycosylase [FPG]). The results showed that exposure to validamycin A, especially at higher doses (1 and 2.5\u00a0mM), induced DNA impairment in neuroblasts as observed by Comet assay. Both larvae and adults exhibited behavioral changes and produced reactive oxygen species. Most importantly, this research represents a pioneering effort to report neurogenotoxicity data specifically in <jats:italic>Drosophila<\/jats:italic> larval neuroblasts, thus underscoring the importance of this species as a testing model in exploring the biological impacts of validamycin A. The in vivo findings from the experiments are a valuable and novel addition to the existing validamycin A neurogenotoxicity database.<\/jats:p>","DOI":"10.1002\/jat.4547","type":"journal-article","created":{"date-parts":[[2023,9,22]],"date-time":"2023-09-22T00:03:34Z","timestamp":1695341014000},"page":"355-370","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["In vivo evaluation of the neurogenotoxic effects of exposure to validamycin A in neuroblasts of <scp><i>Drosophila melanogaster<\/i><\/scp> larval brain"],"prefix":"10.1002","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8045-8641","authenticated-orcid":false,"given":"Fatma","family":"Turna Demir","sequence":"first","affiliation":[{"name":"Massachusetts General Hospital Harvard Medical School  Boston Massachusetts USA"},{"name":"Department of Medical Services and Techniques, Medical Laboratory Techniques Programme, Vocational School of Health Services Antalya Bilim University  Antalya Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2146-7385","authenticated-orcid":false,"given":"E\u015fref","family":"Demir","sequence":"additional","affiliation":[{"name":"F.M. 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