Effects of curcumin to counteract levodopa-induced toxicity in zebrafish

ABSTRACTParkinson's disease (PD) is a neurodegenerative disorder characterized by motor dysfunction due to the death of dopaminergic neurons in the substantia nigra pars compacta. Currently, treatment of PD has focused on increasing dopamine levels, using a dopamine precursor, levodopa (L-DOPA) or stimulation of dopaminergic receptors. Prolonged use of L-DOPA is associated with the occurrence of motor complications and dyskinesia, attributed to neurotoxic effects of this drug. The aim of this study was to investigate the effects of curcumin (CUR), a lipophilic polyphenol, to counteract L-DOPA induced toxicity. Zebrafish larvae were pre-treated with CUR (0.05 µM) or vehicle dimethyl sulfoxide (DMSO) for 24 hr and subsequently exposed to L-DOPA (1 mM) or vehicle. Immediately and 24 hr after L-DOPA exposure, spontaneous swimming and dark/light behavioral tests were performed. In addition, levels of reactive oxygen species (ROS) and lipid peroxidation products were determined at the end of treatment. CUR significantly improved the motor impairment induced by 24 hr L-DOPA treatment, and reduced levels of ROS and lipoperoxidation products in zebrafish larvae. In conclusion, our results suggest that CUR acts as a neuroprotector against toxicity initiated by L-DOPA. Evidence suggests the observed effects of CUR are associated with its antioxidant properties.KEYWORDS: Parkinson´s diseaseneurotoxicityantioxidantpolyphenolsneuroprotection Disclosure statementNo potential conflict of interest was reported by the author(s).Data availability statementThe data that support the findings of this study are available from the corresponding author, [M.A.H] by e-mail (marianaappel@gmail.com), upon reasonable request.Additional informationFundingThis study was supported by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brasil (CAPES) [Finance Code 001]. M.A.H receives Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) fellow [research grant 309840/2022-8].