Selenium-induced antioxidant protection recruits modulation of thioredoxin reductase during excitotoxic/pro-oxidant events in the rat striatum

► The time-course effect of selenium was evaluated on QUIN toxicity in rat striatum. ► Se induced TrxR and protected against oxidative toxicity of QUIN. ► QUIN stimulated TrxR localization (but not enzyme activation) at early time points. ► Evidence suggests that Se-modulated Trx/TrxR contributes to protection. 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 (Na2SO3, 0.625mg/kg/day, i.p., administered for 5 consecutive days) in the toxic pattern produced by a single infusion of QUIN (240nmol/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 30min and 2h post-lesion, evidenced by immunohistochemistry), to further stimulate a delayed protein activation (at 24h) 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.