title: Sulforaphane reduces the alterations induced by quinolinic acid: modulation of glutathione levels.
abstract: Glutamate-induced excitotoxicity involves a state of acute oxidative stress, which is a crucial event during neuronal degeneration and is part of the physiopathology of neurodegenerative diseases. In this work, we evaluated the ability of sulforaphane (SULF), a natural dietary isothiocyanate, to induce the activation of transcription factor Nrf2 (a master regulator of redox state in the cell) in a model of striatal degeneration in rats infused with quinolinic acid (QUIN). Male Wistar rats received SULF (5mg/kg, i.p.) 24h and 5min before the intrastriatal infusion of QUIN. SULF increased the reduced glutathione (GSH) levels 4h after QUIN infusion, which was associated with its ability to increase the activity of glutathione reductase (GR), an antioxidant enzyme capable to regenerate GSH levels at 24h. Moreover, SULF treatment increased glutathione peroxidase (GPx) activity, while no changes were observed in γ-glutamyl cysteine ligase (GCL) activity. SULF treatment also prevented QUIN-induced oxidative stress (measured by oxidized proteins levels), the histological damage and the circling behavior. These results suggest that the protective effect of SULF could be related to its ability to preserve GSH levels and increase GPx and GR activities.
authors.affiliation: Laboratorio de Patología Vascular Cerebral, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Mexico City 14269, Mexico.
authors.forename: R A
authors.initials: RA
authors.lastname: Santana-Martínez
authors.affiliation: Departamento de Neuroquímica, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Mexico City 14269, Mexico.
authors.forename: S
authors.initials: S
authors.lastname: Galván-Arzáte
authors.affiliation: Laboratorio de Patología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City 14000, Mexico.
authors.forename: R
authors.initials: R
authors.lastname: Hernández-Pando
authors.affiliation: Laboratorio de Patología Vascular Cerebral, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Mexico City 14269, Mexico.
authors.forename: M E
authors.initials: ME
authors.lastname: Chánez-Cárdenas
authors.affiliation: Departamento de Biología de la Reproducción, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City 14000, Mexico.
authors.forename: E
authors.initials: E
authors.lastname: Avila-Chávez
authors.affiliation: Laboratorio de Patología Vascular Cerebral, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Mexico City 14269, Mexico.
authors.forename: G
authors.initials: G
authors.lastname: López-Acosta
authors.affiliation: Facultad de Química, Universidad Nacional Autónoma de México, Mexico City, Mexico.
authors.forename: J
authors.initials: J
authors.lastname: Pedraza-Chaverrí
authors.affiliation: Laboratorio de Aminoácidos Excitadores, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Mexico City 14269, Mexico.
authors.forename: A
authors.initials: A
authors.lastname: Santamaría
authors.affiliation: Laboratorio de Patología Vascular Cerebral, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Mexico City 14269, Mexico. Electronic address: maldonado.perla@gmail.com.
authors.forename: P D
authors.initials: PD
authors.lastname: Maldonado
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism*; D005980:Glutathione Reductase / Q000378:metabolism; D017879:Isothiocyanates / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D019636:Neurodegenerative Diseases / Q000378:metabolism; D017378:Quinolinic Acid / Q000378:metabolism*; D017208:Rats, Wistar; D013454:Sulfoxides
chemical_list: D016588:Anticarcinogenic Agents; D017879:Isothiocyanates; D013454:Sulfoxides; D005980:Glutathione Reductase; D017378:Quinolinic Acid; C016766:sulforaphane; D005978:Glutathione
keywords: excitotoxicity; glutathione; neuroprotection; quinolinic acid; sulforaphane