Targeting redox metabolism: the perfect storm induced by acrylamide poisoning in the brain
Demetrio Raldúa, Marta Casado, Eva Prats, Melissa Faria, Francesc Puig‐Castellví, Yolanda Pérez, Ignacio Alfonso, Chuan-Yu Hsu, Mark A. Arick, Natàlia García‐Reyero, Tamar Ziv, Shani Ben-Lulu, Arie Admon, Benjamı́n Piña
Abstract
Exposure to acrylamide may lead to different neurotoxic effects in humans and in experimental animals. To gain insights into this poorly understood type of neurotoxicological damage, we used a multi-omic approach to characterize the molecular changes occurring in the zebrafish brain exposed to acrylamide at metabolite, transcript and protein levels. We detected the formation of acrylamide adducts with thiol groups from both metabolites and protein residues, leading to a quasi-complete depletion of glutathione and to the inactivation of different components of the thioredoxin system. We propose that the combined loss-of-function of both redox metabolism-related systems configure a perfect storm that explains many acrylamide neurotoxic effects, like the dysregulation of genes related to microtubules, presynaptic vesicle alteration, and behavioral alterations. We consider that our mechanistical approach may help developing new treatments against the neurotoxic effects of acrylamide and of other neurotoxicants that may share its toxic mode of action.