Xilofuranosídeos contendo selênio e telúrio atenuam a toxicidade induzida por Mn em Caenorhabditis elegans através da modulação da via DAF-16/FOXO

Abstract

Organoselenium and organotellurium compounds have been reported as antioxidant in several models of oxidative stress. Nevertheless, because of the complexity of mammalian models, it has been difficult to determine the molecular pathways and specific proteins that are modulated in response to treatments with these compounds. In this context, the present study investigated the effects and action mechanisms of a novel class of organic compounds of selenium (Se) and tellurium (Te) called Xylofuranosides, utilizing as an alternative experimental model the nematode Caenorhabditis elegans (C. elegans), that affords easy genetic manipulations, green fluorescent protein tagging and in vivo live analysis of toxicity. In this study, we challenged worms to manganese (Mn), a known pro oxidizing agent, as there is abundant evidence pointing out to oxidative stress in mediating its toxicity. We investigated the efficacy of Se- and Te- xylofuranosides in reversing and/or protecting the worms from Mn-induced toxicity. In addition, we investigated their putative mechanism of action. First, we found the lethal dose 50% (LD50) for the compounds, which were 0.73mM and 0.8mM for Se and Te compound, respectively. This was followed by studies on the ability of the xylofuranosides to afford protection against Mn-induced toxicity. Both Se and Te-xylofuranosides reversed the Mn-lethality, decreased reactive oxygen species (ROS) production and increased the expression of superoxide dismutase (SOD-3), indicating that the increased survival was associated with decreased oxidative stress. Furthermore, we observed that the xylofuranosides induced nuclear translocation of the transcriptional factor DAF-16/FOXO, which in the worm is known to regulate stress responsiveness, aging, metabolism and the expression of SOD-3, as verified in this study. These findings x suggest that xylofuranosides attenuate Mn-induced ROS generation by regulating the DAF-16/FOXO signaling pathway.