Neuroprotective action of Eicosapentaenoic (EPA) and Docosahexaenoic (DHA) acids on Paraquat intoxication in Drosophila melanogaster

• Published in: Neurotoxicology (Park Forest South) Vol. 70; pp. 154 - 160
• Main Authors: de Oliveira Souza, Anderson, Couto-Lima, Carlos Antônio, Catalão, Carlos Henrique Rocha, Santos-Júnior, Nilton Nascimento, dos Santos, Júlia Fernanda, da Rocha, Maria Jose Alves, Alberici, Luciane Carla
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.01.2019; Elsevier BV
• Subjects: Amyloid; Animal models; Citrate synthase; Dichlorides; Diet; Docosahexaenoic and eicosapentaenoic acids; Drosophila melanogaster; Electron transport chain; Embryos; Fatty acids; Fibrils; Herbicides; Hydrogen peroxide; Ingestion; Insects; Intoxication; Lactic acid; Metabolism; Mitochondria; Mitochondrial dysfunction; Neurodegeneration; Neurodegenerative diseases; Neurological diseases; Neuroprotection; Paraquat; Proteins; Secretase; Spectrin; Toxicity; Viability; Neuroprotection; Paraquat; Mitochondrial dysfunction; Docosahexaenoic and eicosapentaenoic acids; Drosophila melanogaster
• ISSN: 0161-813X; 1872-9711
• DOI: 10.1016/j.neuro.2018.11.013

•Paraquat ingestion induces mitochondrial dysfunction in fly brain.•Paraquat ingestion induces the loss of ELAV and α-spectrin.•Paraquat ingestion increases gamma-secretase activity and amyloid fibrils.•EPA/DHA prevents mitochondrial dysfunction induced by Paraquat in fly brain.•EPA/DHA prevents toxic effects induced by Paraquat in fly brain. Several studies have shown the protective effects of dietary enrichment of omega-3 (ω-3) long-chain fatty acids in several animal models of neurodegenerative diseases. Here we investigate if eicosapentaenoic (EPA) and Docosahexaenoic (DHA) acids (ω-3) protect against neurodegeneration mediated by the exposure to a widely used herbicide Paraquat (PQ) (1,1ʹ-dimethyl-4-4ʹ-bipyridinium dichloride), focusing on mitochondrial metabolism using Drosophila melanogaster as a model. Dietary ingestion of PQ for 3 days resulted in the loss of citrate synthase content, respiratory capacity impairment and exacerbated H2O2 production per mitochondrial unit related to complex I dysfunction, and high lactate accumulation in fly heads. PQ intoxication lead to 1) the loss of ELAV (embryonic lethal abnormal vision) and α-spectrin, essential proteins of neuronal viability and synaptic stability; 2) increased gamma-secretase activity, an enzyme related to APP release; and 3) increased the amyloid fibrils contents. All these toxic effects induced by PQ were prevented by concomitant dietary ingestion of EPA/DHA, suggesting that a neuroprotective effect of ω-3 also involves mitochondrial protection. In conclusion, concomitant EPA and DHA ingestion protects against PQ-induced neuronal and mitochondrial dysfunctions frequently found in neurodegenerative processes reinforcing its protective role against environmental neurodegenerative diseases.