Possible involvement of transcriptional activation of nuclear factor erythroid 2-related factor 2 (Nrf2) in the protective effect of caffeic acid on paraquat-induced oxidative damage in Drosophila melanogaster

Paraquat (PQ) is a widely used herbicide with no antidote which is implicated in the pathogenesis of the Parkinson's disease. The present study then investigated the potential of caffeic acid (CA), a known antioxidant, cardioprotective and neuroprotective molecule to counteract oxidative stress...

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Published in:Pesticide biochemistry and physiology 2019-06, Vol.157, p.161-168
Main Authors: dos Santos Nunes, Ricardo Gomes, Pereira, Pedro Silvino, Elekofehinti, Olusola Olalekan, Fidelis, Kleber Ribeiro, da Silva, Cícera Simoni, Ibrahim, Mohammad, Barros, Luiz Marivando, da Cunha, Francisco Assis Bezerra, Lukong, Kiven Erique, de Menezes, Irwin Rose Alencar, Tsopmo, Apollinaire, Duarte, Antonia Eliene, Kamdem, Jean Paul
Format: Article
Language:English
Subjects:
Caffeic acid
Drosophila melanogaster
Oxidative stress
Paraquat poisoning
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Summary:Paraquat (PQ) is a widely used herbicide with no antidote which is implicated in the pathogenesis of the Parkinson's disease. The present study then investigated the potential of caffeic acid (CA), a known antioxidant, cardioprotective and neuroprotective molecule to counteract oxidative stress mediated by PQ. In addition, molecular docking was performed to understand the mechanism underlying the inhibitory effect of CA against PQ poisoning. The fruit fly, Drosophila melanogaster, was exposed to PQ (0.44 mg/g of diet) in the absence or presence of CA (0.25, 0.5, 1 and 2 mg/g of died) for 7 days. Data showed that PQ-fed flies had higher incidence of mortality which was associated with mitochondrial dysfunction, increased free Fe(II) content and lipid peroxidation when compared to the control. Co-exposure with CA reduced mortality and markedly attenuated biochemical changes induced by PQ. The mechanism investigated using molecular docking revealed a strong interaction (−6.2 Kcal/mol) of CA with D. melanogaster transcriptional activation of nuclear factor erythroid 2-related factor 2 (Nrf2). This was characterized by the binding of CA to keap-1 domain of Nrf2. Taking together these results indicate the protective effect of CA against PQ-induced oxidative damage in D. melanogaster was likely through its coordination which hinders Nrf2-keap-1 binding leading to an increase of the antioxidant defense system. Graphical abstract [Display omitted] •Caffeic acid (CA) role on paraquat (PQ)-induced oxidative stress was investigated in Drosophila melanogaster (DM).•PQ exposure caused higher incidence of mortality, increased lipid peroxidation and free Fe2+ content.•CA co-exposure alleviated biochemical alterations and optimized SDH activity.•Antioxidative mechanim of CA is via its strong interaction (−6.2 Kcal/mol) with Nrf2 from DM.
ISSN:0048-3575
1095-9939
DOI:10.1016/j.pestbp.2019.03.017