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

摘要

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.