Protective effect of spin trap agent, N-tert-butyl-alpha-phenylnitrone on hyperoxia-induced oxidative stress and its potential as a nitric oxide donor.
We have previously suggested that the spin trap agent, N-tert-butyl-alpha-phenylnitrone (PBN) can function not only as an antioxidant but also as a nitric oxide (NO) donor. To characterize the pharmacological activities of PBN against oxidative damage, we examined the effect of PBN on NO generation under hyperoxic conditions. The formation of NO in mice exposed to 95% oxygen was determined using a NOx analyzer and electron spin resonance (ESR). Levels of NOx, an oxidative product of NO, increased in the blood of mice under these conditions. However, the increase was returned to a normal level by the NOS (nitric oxide synthase) inhibitor, L-NMMA, indicating that the NO was formed via a biosynthetic pathway. In addition, ESR spectra of the liver and brain of control and experimental mice that were measured using Fe(DETC)2 as an NO trap reagent showed strong ESR signals from NO complexes in the livers of mice exposed to 95% oxygen. When examining the effect of PBN in mice, PBN reduced the NOx formation in the blood under the same hyperoxic conditions. In addition, the ESR intensity of the NO complex was weaker in the PBN-treated mice than in the non-treated mice, showing that PBN possess anti-inflammatory properties. However, under a normal atmosphere, NOx and ESR analyses showed that NO levels increased in PBN-treated mice but not in control mice. These findings suggested that PBN functions as an NO donor under specific physiological conditions. PBN appears to protect against hyperoxia-induced NO toxicity by anti-inflammatory action rather than by serving as an NO donor.
Saito
Kieko
K
Institute for Environmental Sciences, University of Shizuoka, Japan. saitok@smail.u.shizuoka-ken.ac.jp
Yoshioka
Hisashi
H
D000818:Animals; D001921:Brain / Q000187:drug effects; D003497:Cyclic N-Oxides; D004578:Electron Spin Resonance Spectroscopy; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D018496:Hyperoxia / Q000378:metabolism*; D008099:Liver / Q000187:drug effects; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009589:Nitrogen Oxides / Q000378:metabolism* / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D013113:Spin Labels; D019097:Spin Trapping; D019323:omega-N-Methylarginine / Q000494:pharmacology
D003497:Cyclic N-Oxides; D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D009589:Nitrogen Oxides; D013113:Spin Labels; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; C029217:phenyl-N-tert-butylnitrone; D019001:Nitric Oxide Synthase