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NAD(P)H oxidase contributes to neurotoxicity in an excitotoxic/prooxidant model of Huntington's disease in rats: protective role of apocynin.
J Neurosci Res. 2010 Feb 15; 88(3):620-9.JN

Abstract

Intrastriatal injection of quinolinic acid (QUIN) to rodents reproduces some biochemical, morphological, and behavioral characteristics of Huntington's disease. NAD(P)H oxidase is an enzymatic complex that catalyzes superoxide anion (O(2).(-)) production from O(2) and NADPH. The present study evaluated the role of NAD(P)H oxidase in the striatal damage induced by QUIN (240 nmol/microl) in adult male Wistar rats by means of apocynin (APO; 5 mg/kg i.p.), a specific NAD(P)H oxidase inhibitor. Rats were given APO 30 min before and 1 hr after QUIN injection or only 30 min after QUIN injection. NAD(P)H oxidase activity was measured in striatal homogenates by O2(*)(-) production. QUIN infusion to rats significantly increased striatal NAD(P)H oxidase activity (2 hr postlesion), whereas APO treatments decreased the QUIN-induced enzyme activity (2 hr postlesion), lipid peroxidation (3 hr postlesion), circling behavior (6 days postlesion), and histological damage (7 days postlesion). The addition of NADH to striatal homogenates increased NAD(P)H oxidase activity in striata from QUIN-treated animals but not from sham rats. Interestingly, O2(*)(-) production in QUIN-lesioned striata was unaffected by the addition of substrates for intramitochondrial O2(*)(-) production, xanthine oxidase and nitric oxide synthase, suggesting that NAD(P)H oxidase may be the main source of O2(*)(-) in QUIN-treated rats. Moreover, the administration of MK-801 to rats as a pretreatment resulted in a complete prevention of the QUIN-induced NAD(P)H activation, suggesting that this toxic event is completely dependent on N-methyl-D-aspartate receptor overactivation. Our results also suggest that NAD(P)H oxidase is involved in the pathogenic events linked to excitotoxic/prooxidant conditions.

Authors+Show Affiliations

Laboratorio de Patología Vascular Cerebral, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, México DF, México.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19795371

Citation

Maldonado, P D., et al. "NAD(P)H Oxidase Contributes to Neurotoxicity in an Excitotoxic/prooxidant Model of Huntington's Disease in Rats: Protective Role of Apocynin." Journal of Neuroscience Research, vol. 88, no. 3, 2010, pp. 620-9.
Maldonado PD, Molina-Jijón E, Villeda-Hernández J, et al. NAD(P)H oxidase contributes to neurotoxicity in an excitotoxic/prooxidant model of Huntington's disease in rats: protective role of apocynin. J Neurosci Res. 2010;88(3):620-9.
Maldonado, P. D., Molina-Jijón, E., Villeda-Hernández, J., Galván-Arzate, S., Santamaría, A., & Pedraza-Chaverrí, J. (2010). NAD(P)H oxidase contributes to neurotoxicity in an excitotoxic/prooxidant model of Huntington's disease in rats: protective role of apocynin. Journal of Neuroscience Research, 88(3), 620-9. https://doi.org/10.1002/jnr.22240
Maldonado PD, et al. NAD(P)H Oxidase Contributes to Neurotoxicity in an Excitotoxic/prooxidant Model of Huntington's Disease in Rats: Protective Role of Apocynin. J Neurosci Res. 2010 Feb 15;88(3):620-9. PubMed PMID: 19795371.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - NAD(P)H oxidase contributes to neurotoxicity in an excitotoxic/prooxidant model of Huntington's disease in rats: protective role of apocynin. AU - Maldonado,P D, AU - Molina-Jijón,E, AU - Villeda-Hernández,J, AU - Galván-Arzate,S, AU - Santamaría,A, AU - Pedraza-Chaverrí,J, PY - 2009/10/2/entrez PY - 2009/10/2/pubmed PY - 2010/3/31/medline SP - 620 EP - 9 JF - Journal of neuroscience research JO - J Neurosci Res VL - 88 IS - 3 N2 - Intrastriatal injection of quinolinic acid (QUIN) to rodents reproduces some biochemical, morphological, and behavioral characteristics of Huntington's disease. NAD(P)H oxidase is an enzymatic complex that catalyzes superoxide anion (O(2).(-)) production from O(2) and NADPH. The present study evaluated the role of NAD(P)H oxidase in the striatal damage induced by QUIN (240 nmol/microl) in adult male Wistar rats by means of apocynin (APO; 5 mg/kg i.p.), a specific NAD(P)H oxidase inhibitor. Rats were given APO 30 min before and 1 hr after QUIN injection or only 30 min after QUIN injection. NAD(P)H oxidase activity was measured in striatal homogenates by O2(*)(-) production. QUIN infusion to rats significantly increased striatal NAD(P)H oxidase activity (2 hr postlesion), whereas APO treatments decreased the QUIN-induced enzyme activity (2 hr postlesion), lipid peroxidation (3 hr postlesion), circling behavior (6 days postlesion), and histological damage (7 days postlesion). The addition of NADH to striatal homogenates increased NAD(P)H oxidase activity in striata from QUIN-treated animals but not from sham rats. Interestingly, O2(*)(-) production in QUIN-lesioned striata was unaffected by the addition of substrates for intramitochondrial O2(*)(-) production, xanthine oxidase and nitric oxide synthase, suggesting that NAD(P)H oxidase may be the main source of O2(*)(-) in QUIN-treated rats. Moreover, the administration of MK-801 to rats as a pretreatment resulted in a complete prevention of the QUIN-induced NAD(P)H activation, suggesting that this toxic event is completely dependent on N-methyl-D-aspartate receptor overactivation. Our results also suggest that NAD(P)H oxidase is involved in the pathogenic events linked to excitotoxic/prooxidant conditions. SN - 1097-4547 UR - https://www.unboundmedicine.com/medline/citation/19795371/NAD_P_H_oxidase_contributes_to_neurotoxicity_in_an_excitotoxic/prooxidant_model_of_Huntington's_disease_in_rats:_protective_role_of_apocynin_ L2 - https://doi.org/10.1002/jnr.22240 DB - PRIME DP - Unbound Medicine ER -