Colonnello, AlineAguilera-Portillo, GabrielaRubio-Lopez, Leonardo CRobles-Bañuelos, BenjaminRangel-Lopez, EdgarCortez-Nuñez, SamariaEvaristo-Priego, YadiraSilva-Palacios, AlejandroGalvan-Arzate, SoniaGarcia-Contreras, RodolfoTunez, IsaacChen, PanAschner, MichaelSantamaria, Abel2023-02-082023-02-082019-10-25Colonnello A, Aguilera-Portillo G, Rubio-López LC, Robles-Bañuelos B, Rangel-López E, Cortez-Núñez S, et al. Comparing the Neuroprotective Effects of Caffeic Acid in Rat Cortical Slices and Caenorhabditis elegans: Involvement of Nrf2 and SKN-1 Signaling Pathways. Neurotox Res. 2020 Feb;37(2):326-337.http://hdl.handle.net/10668/14749Caffeic acid (CA) is a hydroxycinnamic acid derivative and polyphenol with antioxidant and anti-inflammatory activities. The neuroprotective properties of CA still need detailed characterization in different biological models. Here, the antioxidant and neuroprotective effects of CA were compared in in vitro and in vivo neurotoxic models. Biochemical outcomes of cell dysfunction, oxidative damage, and transcriptional regulation were assessed in rat cortical slices, whereas endpoints of physiological stress and motor alterations were characterized in Caenorhabditis elegans (C. elegans). In rat cortical slices, CA (100 μM) prevented, in a differential manner, the loss of reductive capacity, the cell damage, and the oxidative damage induced by the excitotoxin quinolinic acid (QUIN, 100 μM), the pro-oxidant ferrous sulfate (FeSO4, 25 μM), and the dopaminergic toxin 6-hydroxydopamine (6-OHDA, 100 μM). CA also restored the levels of nuclear factor erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE; a master antioxidant regulatory pathway) binding activity affected by the three toxins. In wild-type (N2) of C. elegans, but not in the skn-1 KO mutant strain (worms lacking the orthologue of mammalian Nrf2), CA (25 mM) attenuated the loss of survival induced by QUIN (100 mM), FeSO4 (15 mM), and 6-OHDA (25 mM). Motor alterations induced by the three toxic models in N2 and skn-1 KO strains were prevented by CA in a differential manner. Our results suggest that (1) CA affords partial protection against different toxic insults in mammalian brain tissue and in C. elegans specimens; (2) the Nrf2/ARE binding activity participates in the protective mechanisms evoked by CA in the mammalian cortical tissue; (3) the presence of the orthologous skn-1 pathway is required in the worms for CA to exert protective effects; and (4) CA exerts antioxidant and neuroprotective effects through homologous mechanisms in different species.enAntioxidant defenseCaenorhabditis elegansCaffeic acidMammal CNSNeuroprotectionNrf2 pathwayTranscriptional regulationskn-1 pathwayAnimalsAnimals, Genetically ModifiedCaenorhabditis elegansCaenorhabditis elegans ProteinsCaffeic AcidsCerebral CortexDNA-Binding ProteinsDose-Response Relationship, DrugMaleNF-E2-Related Factor 2Neuroprotective AgentsOrgan Culture TechniquesRatsRats, WistarSignal TransductionSpecies SpecificityTranscription Factorsresearch article31773641open accessAnimalesCaenorhabditis elegansCorteza cerebralEspecificidad de la especieFactor 2 relacionado con NF-E2Factores de transcripciónFármacos neuroprotectoresProteínas de Caenorhabditis elegansProteínas de unión al ADNRelación dosis-respuesta a drogaÁcidos cafeicos10.1007/s12640-019-00133-81476-3524PMC6994368https://europepmc.org/articles/pmc6994368?pdf=renderhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6994368/pdf