title: Antioxidant properties of Neu2000 on mitochondrial free radicals and oxidative damage.
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.
authors.affiliation: Physical Medicine and Rehabilitation, University of Kentucky, Lexington, KY 40536-0509, United States.
authors.forename: Nishant P
authors.initials: NP
authors.lastname: Visavadiya
authors.forename: Melanie L
authors.initials: ML
authors.lastname: McEwen
authors.forename: Jignesh D
authors.initials: JD
authors.lastname: Pandya
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Sullivan
authors.forename: Byoung Joo
authors.initials: BJ
authors.lastname: Gwag
authors.forename: Joe E
authors.initials: JE
authors.lastname: Springer
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D005260:Female; D005464:Fluorobenzenes / Q000494:pharmacology*; D005609:Free Radicals / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D066298:In Vitro Techniques; D007501:Iron / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D050050:Protein Carbonylation / Q000187:drug effects; D051381:Rats; D020318:Rats, Long-Evans; D012459:Salicylates / Q000494:pharmacology*; D013116:Spinal Cord / Q000378:metabolism; D062368:meta-Aminobenzoates / Q000494:pharmacology*
chemical_list: C519903:2-hydroxy-5-(2,3,5,6-tetrafluoro-4-trifluoromethyl-benzylamino)benzoic acid; D000975:Antioxidants; D005464:Fluorobenzenes; D005609:Free Radicals; D018696:Neuroprotective Agents; D012459:Salicylates; D062368:meta-Aminobenzoates; D009569:Nitric Oxide; D007501:Iron; D005978:Glutathione