title: Selenium-induced antioxidant protection recruits modulation of thioredoxin reductase during excitotoxic/pro-oxidant events in the rat striatum.
abstract: Selenium (Se) is a crucial element exerting antioxidant and neuroprotective effects in different toxic models. It has been suggested that Se acts through selenoproteins, of which thioredoxin reductase (TrxR) is relevant for reduction of harmful hydroperoxides and maintenance of thioredoxin (Trx) redox activity. Of note, the Trx/TrxR system remains poorly studied in toxic models of degenerative disorders. Despite previous reports of our group have demonstrated a protective role of Se in the excitotoxic/pro-oxidant model induced by quinolinic acid (QUIN) in the rat striatum (Santamaría et al., 2003, 2005), the precise mechanism(s) by which Se is inducing protection remains unclear. In this work, we characterized the time course of protective events elicited by Se as pretreatment (Na(2)SO(3), 0.625 mg/kg/day, i.p., administered for 5 consecutive days) in the toxic pattern produced by a single infusion of QUIN (240 nmol/μl) in the rat striatum, to further explore whether TrxR is involved in the Se-induced protection and how is regulated. Se attenuated the QUIN-induced early reactive oxygen species formation, lipid peroxidation, oxidative damage to DNA, loss of mitochondrial reductive capacity and morphological alterations in the striatum. Our results also revealed a novel pattern in which QUIN transiently stimulated an early TrxR cellular localization/distribution (at 30 min and 2 h post-lesion, evidenced by immunohistochemistry), to further stimulate a delayed protein activation (at 24 h) in a manner likely representing a compensatory response to the oxidative damage in course. In turn, Se induced an early stimulation of TrxR activity and expression in a time course that "matches" with the reduction of the QUIN-induced oxidative damage, suggesting that the Trx/TrxR system contributes to the resistance of nerve tissue to QUIN toxicity.
authors.affiliation: Laboratorio de Patología Vascular Cerebral, Instituto Nacional de Neurología y Neurocirugía, Mexico 14269, Mexico.
authors.forename: Perla D
authors.initials: PD
authors.lastname: Maldonado
authors.forename: Verónica
authors.initials: V
authors.lastname: Pérez-De La Cruz
authors.forename: Mónica
authors.initials: M
authors.lastname: Torres-Ramos
authors.forename: Carlos
authors.initials: C
authors.lastname: Silva-Islas
authors.forename: Ramón
authors.initials: R
authors.lastname: Lecona-Vargas
authors.forename: Rafael
authors.initials: R
authors.lastname: Lugo-Huitrón
authors.forename: Tonali
authors.initials: T
authors.lastname: Blanco-Ayala
authors.forename: Perla
authors.initials: P
authors.lastname: Ugalde-Muñiz
authors.forename: Gustavo Ignacio
authors.initials: GI
authors.lastname: Vázquez-Cervantes
authors.forename: Teresa I
authors.initials: TI
authors.lastname: Fortoul
authors.forename: Syed F
authors.initials: SF
authors.lastname: Ali
authors.forename: Abel
authors.initials: A
authors.lastname: Santamaría
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D015153:Blotting, Western; D002452:Cell Count; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000494:pharmacology; D007150:Immunohistochemistry; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D017072:Neostriatum / Q000201:enzymology* / Q000473:pathology; D009498:Neurotoxins / Q000633:toxicity*; D016877:Oxidants / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D017378:Quinolinic Acid / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D018036:Selenium Compounds / Q000494:pharmacology*; D013880:Thioredoxin-Disulfide Reductase / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D009498:Neurotoxins; D016877:Oxidants; D017382:Reactive Oxygen Species; D018036:Selenium Compounds; D000080242:8-Hydroxy-2'-Deoxyguanosine; D013880:Thioredoxin-Disulfide Reductase; D017378:Quinolinic Acid; D003849:Deoxyguanosine