Protective effect of tert-butylhydroquinone on the quinolinic-acid-induced toxicity in rat striatal slices: role of the Nrf2-antioxidant response element pathway.
Tert-butylhydroquinone (tBHQ) is a xenobiotic with reported antioxidant properties. tBHQ has been shown to induce nuclear translocation of the transcription factor NF-E2-related factor 2 (Nrf2) to further activate the antioxidant response element (ARE). In turn, the Nrf2/ARE pathway is responsible for the induction of phase 2 antioxidant enzymes that detoxify oxidant promoters from different toxic insults. In this work, the antioxidant and protective actions of tBHQ were explored for the first time on different biomarkers of the neurotoxic model produced by the excitotoxic and pro-oxidant molecule quinolinic acid (QUIN) in rat striatal slices. For comparison purposes, 3-nitropropionic acid was used as reference model. Our results show that tBHQ (25 μM) prevented the QUIN-induced lipid peroxidation and mitochondrial dysfunction. In addition, tBHQ enhanced glutathione-S-transferase activity, partially recovering its depletion induced by QUIN treatment. Our results also demonstrated that tBHQ was able to induce nuclear accumulation of Nrf2 and further antioxidant protection: while QUIN alone decreased the nuclear Nrf2, a treatment with tBHQ preserved the nuclear levels Nrf2 in the presence of QUIN. Therefore, the tBHQ-mediated Nrf2/ARE induction constitutes a signaling-mediated antioxidant strategy and therapeutic tool to be tested in different neurotoxic models.
Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad de Córdoba, Córdoba, Spain.
Inmaculada
I
Tasset
Verónica
V
Pérez-De La Cruz
Diana
D
Elinos-Calderón
Paul
P
Carrillo-Mora
Irma Gabriela
IG
González-Herrera
Armando
A
Luna-López
Mina
M
Konigsberg
José
J
Pedraza-Chaverrí
Perla D
PD
Maldonado
Syed F
SF
Ali
Isaac
I
Túnez
Abel
A
Santamaría
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006873:Hydroquinones / Q000494:pharmacology*; D066298:In Vitro Techniques; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D017378:Quinolinic Acid / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects*; D013778:Tetrazolium Salts / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism
D000975:Antioxidants; D006873:Hydroquinones; D051267:NF-E2-Related Factor 2; D013778:Tetrazolium Salts; D013844:Thiazoles; D008315:Malondialdehyde; C018855:2-tert-butylhydroquinone; C022616:thiazolyl blue; D017378:Quinolinic Acid