Evidence of acrylamide-induced behavioral deficit, mitochondrial dysfunction and cell death in Drosophila melanogaster

• Published in: Comparative biochemistry and physiology. Toxicology & pharmacology 2024-10, Vol.284, p.109971, Article 109971
• Main Authors: Farodoye, Oluwabukola Mary, Otenaike, Titilayomi Ayomide, Loreto, Julia Sepel, Adedara, Adeola Oluwatosin, Silva, Monica Medeiros, Barbosa, Nilda Vargas, Rocha, Joao Batista Teixeira da, Abolaji, Amos Olalekan, Loreto, Elgion Lucio Silva
• Format: Article
• Language: English
• Subjects: Acrylamide; Cellular metabolic activity; Drosophila melanogaster; Mitochondria; Oxidative stress
• ISSN: 1532-0456
• DOI: 10.1016/j.cbpc.2024.109971

Acrylamide (ACR), a ubiquitous compound with diverse route of exposure, has been demonstrated to have detrimental effects on human and animal health. The mechanisms underlying its toxicity is multifaceted and not fully elucidated. This study aims to provide further insight into novel pathways underlying ACR toxicity by leveraging on Drosophila melanogaster as a model organism. The concentrations of acrylamide (25, 50 and 100 mg/kg) and period of exposure (7-days) used in this study was established through a concentration response curve. ACR exposure demonstrably reduced organismal viability, evidenced by decline in survival rate, offspring emergence and deficits in activity, sleep and locomotory behaviors. Using a high-resolution respirometry assay, the role of mitochondria respiratory system in ACR-mediated toxicity in the flies was investigated. Acrylamide caused dysregulation in mitochondrial bioenergetics and respiratory capacity leading to an impaired OXPHOS activity and electron transport, ultimately contributing to the pathological process of ACR-toxicity. Furthermore, ACR exacerbated apoptosis and induced oxidative stress in D. melanogaster. The up-regulation of mRNA transcription of Reaper, Debcl and Dark genes and down-regulation of DIAP1, an ubiquitylation catalyzing enzyme, suggests that ACR promotes apoptosis through disruption of caspase and pro-apoptotic protein ubiquitination and a mitochondria-dependent pathway in Drosophila melanogaster. Conclusively, this study provides valuable insights into the cellular mechanism underlying ACR-mediated toxicity. Additionally, our study reinforces the utility of D. melanogaster as a translational tool for elucidating the complex mechanisms of ACR toxicity. [Display omitted] •Mechanisms of toxicity of acrylamide was evaluated in Drosophila melanogaster.•Acrylamide (ACR) induces decreased survival rate, behavioral deficit and in Drosophila.•ACR impairs the functionality and dynamic of mitochondria in exposed flies by compromising the ETS and OXPHOS machinery•ACR aggravates cellular apoptosis through mitochondria and caspase-dependent pathway in Drosophila melanogaster