NAD(P)H oxidase contributes to neurotoxicity in an excitotoxic/prooxidant model of Huntington's disease in rats: Protective role of apocynin
✍ Scribed by P.D. Maldonado; E. Molina-Jijón; J. Villeda-Hernández; S. Galván-Arzate; A. Santamaría; J. Pedraza-Chaverrí
- Publisher
- John Wiley and Sons
- Year
- 2009
- Tongue
- English
- Weight
- 321 KB
- Volume
- 88
- Category
- Article
- ISSN
- 0360-4012
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✦ Synopsis
Me ´xico
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 Á
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/ll) 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 O 2 Á 2 production. QUIN infusion to rats significantly increased striatal NAD(P)H oxidase activity (2 hr postlesion), whereas APO treatments decreased the QUINinduced 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, O 2 Á 2 production in QUIN-lesioned striata was unaffected by the addition of substrates for intramitochondrial O 2 Á 2 production, xanthine oxidase and nitric oxide synthase, suggesting that NAD(P)H oxidase may be the main source of O 2 Á 2 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 Nmethyl-D-aspartate receptor overactivation. Our results also suggest that NAD(P)H oxidase is involved in the pathogenic events linked to excitotoxic/prooxidant conditions.