RETRACTED: Curcumin restores Nrf2 levels and prevents quinolinic acid-induced neurotoxicity.
Neurological diseases comprise a group of heterogeneous disorders characterized by progressive brain dysfunction and cell death. In the next years, these diseases are expected to constitute a world-wide health problem. Because excitotoxicity and oxidative stress are involved in neurodegenerative diseases, it becomes relevant to describe pharmacological therapies designed to activate endogenous cytoprotective systems. Activation of transcription factor Nrf2 stimulates cytoprotective vitagenes involved in antioxidant defense. In this work, we investigated the ability of the antioxidant curcumin to induce transcription factor Nrf2 in a neurodegenerative model induced by quinolinic acid in rats. Animals were administered with curcumin (400 mg/kg, p.o.) for 10 days, and then intrastriatally infused with quinolinic acid (240 nmol) on day 10 of treatment. Curcumin prevented rotation behavior (6 days post-lesion), striatal morphological alterations (7 days post-lesion) and neurodegeneration (1 and 3 days post-lesion) induced by quinolinic acid. Curcumin also reduced quinolinic acid-induced oxidative stress (measured as protein carbonyl content) at 6 h post-lesion. The protective effects of curcumin were associated to its ability to prevent the quinolinic acid-induced decrease of striatal intra-nuclear Nrf2 levels (30 and 120 min post-lesion), and total superoxide dismutase and glutathione peroxidase activities (1 day post-lesion). Therefore, results of this study support the concept that neuroprotection induced by curcumin is associated with its ability to activate the Nrf2 cytoprotective pathway and to increase the total superoxide dismutase and glutathione peroxidase activities.
Patología Vascular Cerebral, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, México D.F., 14269, México.
Iván
I
Carmona-Ramírez
Abel
A
Santamaría
Julio C
JC
Tobón-Velasco
Marisol
M
Orozco-Ibarra
Irma G
IG
González-Herrera
José
J
Pedraza-Chaverrí
Perla D
PD
Maldonado
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003474:Curcumin / Q000494:pharmacology*; D005979:Glutathione Peroxidase / Q000378:metabolism; D008297:Male; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D020258:Neurotoxicity Syndromes / Q000517:prevention & control*; D018384:Oxidative Stress / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology*; D017378:Quinolinic Acid / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism
D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D020011:Protective Agents; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D017378:Quinolinic Acid; D003474:Curcumin