Apocynin protects against neurological damage induced by quinolinic acid by an increase in glutathione synthesis and Nrf2 levels.
Apocynin (APO) is a well-known NADPH oxidase (NOX) inhibitor. However, several studies have reported its ability to increase glutathione (GSH) levels. Due to GSH is a major non-enzymatic antioxidant in brain, the aim of this study was to evaluate, in the striatum of control and quinolinic acid (QUIN) injected rats, the effect of APO administration on: (1) GSH levels, (2) activity of some enzymes involved in the GSH metabolism, and (3) nuclear factor erythroid-2-related factor 2 (Nrf2) mRNA levels. Animals received QUIN 240nmol in right striatum and APO (5mg/kg, i.p.), 30min before and 60min after intrastriatal injection. APO treatment prevented the QUIN-induced histological damage to the striatum. In control rats, APO treatment increased GSH and Nrf2 mRNA levels and the activities of gamma-glutamylcysteine ligase (γ-GCL), glutathione-S-transferase (GST) and glutathione peroxidase (GPx). On the other hand, APO treatment prevented the QUIN-induced decrease in GSH and Nrf2 levels, and in γ-GCL and GPx activities. These data indicate that APO is able to increase GSH levels and the activity of proteins involved in its metabolism, which could be associated with its ability to increase the Nrf2 mRNA levels.
Laboratorio de Patología Vascular Cerebral, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Av. Insurgentes Sur 3877, Tlalpan, La Fama, CDMX 14269, Mexico. Electronic address: lulicuas@outlook.com.
Silvia
S
Cruz-Álvarez
Laboratorio de Patología Vascular Cerebral, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Av. Insurgentes Sur 3877, Tlalpan, La Fama, CDMX 14269, Mexico. Electronic address: santana_ricardo03@hotmail.com.
Ricardo
R
Santana-Martínez
Departamento de Biología de la Reproducción, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15, Tlalpan, Belisario Domínguez Sección XVI, CDMX 14080, Mexico. Electronic address: euclidesavilac@gmail.com.
Euclides
E
Avila-Chávez
Departamento de Farmacología, Facultad de Medicina, Universidad Nacional Autónoma de México, Av. Universidad 3000, Coyoacán, CDMX 04510, Mexico. Electronic address: dianabarrera@hotmail.com.
Diana
D
Barrera-Oviedo
Departamento de Patología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15, Tlalpan, Belisario Domínguez Sección XVI, CDMX 14080, Mexico. Electronic address: rhdezpando@hotmail.com.
Rogelio
R
Hernández-Pando
Departamento de Biología, Facultad de Química, Universidad Nacional Autónoma de México, Av. Universidad 3000, Coyoacán, CDMX 04510, Mexico. Electronic address: pedrazachaverri@gmail.com.
José
J
Pedraza-Chaverri
Laboratorio de Patología Vascular Cerebral, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Av. Insurgentes Sur 3877, Tlalpan, La Fama, CDMX 14269, Mexico. Electronic address: maldonado.perla@gmail.com.
Perla D
PD
Maldonado
D000098:Acetophenones / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism*; D005979:Glutathione Peroxidase / Q000378:metabolism; D008297:Male; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D017378:Quinolinic Acid / Q000494:pharmacology; D017208:Rats, Wistar
D000098:Acetophenones; D000975:Antioxidants; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; C056165:acetovanillone; D005979:Glutathione Peroxidase; D017378:Quinolinic Acid; D005978:Glutathione
Nrf2 factor; apocynin; glutathione; quinolinic acid