Resveratrol attenuates iron-induced toxicity in a chronic post-treatment paradigm in Caenorhabditis elegans

There is an increase in the number of studies indicating that a disturbance in iron homeostasis is involved in the pathogenesis of neurodegenerative diseases, in which oxidative stress plays an important role. Oxidative stress can be counteracted by bioactive molecules like the flavonoid resveratrol, which acts as scavenging agent, or by modulating enzymes and metabolic signalling pathways, thus depicting the neuroprotective potential. On the other hand, flavonoids, resveratrol included, have been reported to induce an increase in the reactive species production. In this study we aimed to evaluate in vivo the protective potential of resveratrol against iron imbalance using the Caenorhabditis elegans model. We acutely exposed C. elegans to iron and administered resveratrol pre- or post-iron treatment. Iron-treated worms demonstrated a significant decrease in the survival, neuronal change, decreased dehydrogenases activity and ATP levels, and a significant increase in the oxidative stress. Acute pre-exposure to resveratrol potentiated the toxic effect of the metal by reducing ATP levels, while post-iron chronic resveratrol treatment following the iron exposure increased the worms' survival and reduced the generation of reactive species and neuronal damage. In conclusion, our results demonstrated that resveratrol has various protective effects depending on the duration and order of administration, whereby chronic post-iron treatment to resveratrol as an antidote appeared to be a more effective approach.