title: Seleno- and telluro-xylofuranosides attenuate Mn-induced toxicity in C. elegans via the DAF-16/FOXO pathway.
abstract: Organochalcogens are promising pharmacological agents that possess significant biological activities. 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. The nematode worm Caenorhabditis elegans is an alternative experimental model that affords easy genetic manipulations, green fluorescent protein tagging and in vivo live analysis of toxicity. Abundant evidence points to oxidative stress in mediating manganese (Mn)-induced toxicity. In this study we challenged worms with Mn, and investigated the efficacy of inedited selenium- and tellurium-xylofuranosides in reversing and/or protecting the worms from Mn-induced toxicity. In addition, we investigated their putative mechanism of action. First, we determined the lethal dose 50% (LD50) and the effects of the xylofuranosides on various toxic parameters. This was followed by studies on the ability of xylofuranosides to afford protection against Mn-induced toxicity. Both Se- and Te-xylofuranosides increased the expression of superoxide dismutase (SOD-3). Furthermore, we observed that the xylofuranosides induced nuclear translocation of the transcription factor DAF-16/FOXO, which in the worm is known to regulate stress responsiveness, aging and metabolism. These findings suggest that xylofuranosides attenuate toxicity Mn-induced, by regulating the DAF-16/FOXO signaling pathway.
authors.affiliation: Laboraterio do Grupo de Pesquisa em Bioquímica e Toxicologia em Caenorhabditis elegans (GBToxCe), Universidade Federal do Pampa - UNIPAMPA, CEP 97500-970, Uruguaiana, RS, Brazil.
authors.forename: Suzi G N
authors.initials: SG
authors.lastname: Wollenhaupt
authors.affiliation: Laboraterio do Grupo de Pesquisa em Bioquímica e Toxicologia em Caenorhabditis elegans (GBToxCe), Universidade Federal do Pampa - UNIPAMPA, CEP 97500-970, Uruguaiana, RS, Brazil.
authors.forename: Ana Thalita
authors.initials: AT
authors.lastname: Soares
authors.affiliation: Laboraterio do Grupo de Pesquisa em Bioquímica e Toxicologia em Caenorhabditis elegans (GBToxCe), Universidade Federal do Pampa - UNIPAMPA, CEP 97500-970, Uruguaiana, RS, Brazil.
authors.forename: Willian G
authors.initials: WG
authors.lastname: Salgueiro
authors.affiliation: Departamento de Química, Universidade Federal de Santa Maria - UFSM, CEP 97105-900, Santa Maria, RS, Brazil.
authors.forename: Simone
authors.initials: S
authors.lastname: Noremberg
authors.affiliation: Departamento de Química, Universidade Federal de Santa Maria - UFSM, CEP 97105-900, Santa Maria, RS, Brazil.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Reis
authors.affiliation: Departamento de Química, Universidade Federal de Santa Maria - UFSM, CEP 97105-900, Santa Maria, RS, Brazil.
authors.forename: Carine
authors.initials: C
authors.lastname: Viana
authors.affiliation: Departamento de Química, Universidade Federal de Santa Maria - UFSM, CEP 97105-900, Santa Maria, RS, Brazil.
authors.forename: Priscila
authors.initials: P
authors.lastname: Gubert
authors.affiliation: Departamento de Química, Universidade Federal de Santa Maria - UFSM, CEP 97105-900, Santa Maria, RS, Brazil.
authors.forename: Felix A
authors.initials: FA
authors.lastname: Soares
authors.affiliation: Instituto de Química, Universidade Federal do Rio Grande do Sul - UFRGS, CEP 91501-970, Porto Alegre, RS, Brazil.
authors.forename: Ricardo F
authors.initials: RF
authors.lastname: Affeldt
authors.affiliation: Instituto de Química, Universidade Federal do Rio Grande do Sul - UFRGS, CEP 91501-970, Porto Alegre, RS, Brazil.
authors.forename: Diogo S
authors.initials: DS
authors.lastname: Lüdtke
authors.affiliation: Laboratório de Biotecnologia da Reprodução (Biotech), Campus Uruguaiana, Universidade Federal do Pampa - UNIPAMPA, CEP 97500-970, Uruguaiana, RS, Brazil.
authors.forename: Francielli W
authors.initials: FW
authors.lastname: Santos
authors.affiliation: Laboraterio do Grupo de Pesquisa em Bioquímica e Toxicologia em Caenorhabditis elegans (GBToxCe), Universidade Federal do Pampa - UNIPAMPA, CEP 97500-970, Uruguaiana, RS, Brazil.
authors.forename: Cristiane C
authors.initials: CC
authors.lastname: Denardin
authors.affiliation: Division of Clinical Pharmacology and Pediatric Toxicology, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37240, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Aschner
authors.affiliation: Laboraterio do Grupo de Pesquisa em Bioquímica e Toxicologia em Caenorhabditis elegans (GBToxCe), Universidade Federal do Pampa - UNIPAMPA, CEP 97500-970, Uruguaiana, RS, Brazil. Electronic address: avilads1@gmail.com.
authors.forename: Daiana S
authors.initials: DS
authors.lastname: Avila
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000187:drug effects* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D051858:Forkhead Transcription Factors; D008345:Manganese / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism; D018036:Selenium Compounds / Q000494:pharmacology*; D013691:Tellurium / Q000494:pharmacology*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; D051858:Forkhead Transcription Factors; D017382:Reactive Oxygen Species; D018036:Selenium Compounds; D014157:Transcription Factors; C108831:daf-16 protein, C elegans; D008345:Manganese; D013691:Tellurium
keywords: C. elegans; DAF-16; Manganese; Oxidative stress; SOD; Xylofuranoside