The nitrone disodium 2,4-sulphophenyl-N-tert-butylnitrone is without cytoprotective effect on sodium nitroprusside-induced cell death in N1E-115 neuroblastoma cells in vitro.
Disodium 2,4-sulphophenyl-N-tert-butylnitrone (NXY-059) is a novel free radical-trapping compound that is neuroprotective in both rodent and primate models of acute ischaemic stroke. Neuroprotection in vitro by NXY-059 has not been reported previously, and we have now investigated whether such an effect can be detected using a simple cell culture model of neurotoxicity. Neuron-like cells of the neuroblastoma-derived clonal cell line N1E-115 were exposed to the free radical-generating agent sodium nitroprusside (SNP), which produced a concentration-dependent reduction in mitochondrial complex II activity 24 h later (EC(50) approximately 100 micromolar). Cell death induced by SNP (100 micromolar), assessed either by an increased proportion of apoptotic nuclear morphology or by mitochondrial complex II activity, was inhibited by a cocktail of known antioxidants (ascorbate, reduced glutathione, and dithiothreitol, all at 100 micromolar) but not by NXY-059 at a concentration known to be neuroprotective in vivo (300 micromolar). Disodium 2,4-sulphophenyl-N-tert-butylnitrone was also without effect on H(2)O(2)-mediated cytotoxicity. These results support recent data suggesting that in vivo NXY-059 probably acts at the neurovascular unit rather than at an intracellular site as a neuroprotective agent.
Hainsworth
Atticus H
AH
Division of Cardiac and Vascular Sciences, Department of Clinical Neurosciences, St George's University of London, London, UK. a.hainsworth@sgul.ac.uk
Bhuiyan
Nasrin
N
Green
A Richard
AR
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001557:Benzenesulfonates / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D042963:Electron Transport Complex II / Q000037:antagonists & inhibitors / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D051379:Mice; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D009599:Nitroprusside / Q000494:pharmacology*; D016877:Oxidants / Q000494:pharmacology*; D011323:Primates; D020521:Stroke / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology
D001557:Benzenesulfonates; D016166:Free Radical Scavengers; D016877:Oxidants; D009599:Nitroprusside; C120851:disufenton sodium; D006861:Hydrogen Peroxide; D042963:Electron Transport Complex II