1. Antioxidant properties of Neu2000 on mitochondrial free radicals and oxidative damage.
- Author
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Visavadiya NP, McEwen ML, Pandya JD, Sullivan PG, Gwag BJ, and Springer JE
- Subjects
- Animals, Female, Free Radicals metabolism, Glutathione metabolism, In Vitro Techniques, Iron metabolism, Mitochondria metabolism, Nitric Oxide metabolism, Oxidative Stress drug effects, Protein Carbonylation drug effects, Rats, Rats, Long-Evans, Spinal Cord metabolism, Antioxidants pharmacology, Fluorobenzenes pharmacology, Mitochondria drug effects, Neuroprotective Agents pharmacology, Salicylates pharmacology, meta-Aminobenzoates pharmacology
- Abstract
Neu2000 [2-hydroxy-5-(2,3,5,6-tetrafluoro-4 trifluoromethylbenzylamino) benzoic acid] is a dual-acting neuroprotective agent that functions both as a noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist and a free radical scavenger. In the present study, we investigated the scavenging activity of Neu2000 on various classes of reactive oxygen species and reactive nitrogen species (ROS/RNS) as well as its efficacy for reducing free radicals and oxidative stress/damage induced in spinal cord mitochondrial preparations. Neu2000 exerted scavenging activity against superoxide, nitric oxide, and hydroxyl radicals, and efficiently scavenged peroxynitrite. In the mitochondrial studies, Neu2000 markedly inhibited ROS/RNS and hydrogen peroxide levels following antimycin treatment. In addition, Neu2000 effectively scavenged hydroxyl radicals generated by iron(III)-ascorbate, reduced protein carbonyl formation mediated by hydroxyl radicals and peroxynitrite, and prevented glutathione oxidation caused by tert-butyl hydroperoxide in isolated mitochondria. Interestingly, incubation of isolated mitochondria with Neu2000 followed by centrifugation and removal of the supernatant also resulted in a concentration-dependent decrease in lipid peroxidation. This observation suggests that Neu2000 enters mitochondria to target free radicals or indirectly affects mitochondrial function in a manner that promotes antioxidant activity. The results of the present study demonstrate that Neu2000 possesses potent in vitro antioxidant activity due, most likely, to its active phenoxy group., (Copyright © 2012 Elsevier Ltd. All rights reserved.)
- Published
- 2013
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