Reaction of superoxide with nitric oxide to form peroxonitrite in alkaline aqueous solution

Blough, Neil V.; Zafiriou, Oliver C.

doi:10.1021/ic00216a003

Cited by 515 publications

(249 citation statements)

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“…Since nitric oxide is known to be destroyed by 02'-, but not by other oxygen derived radicals (22), 02' -produced from DEP seems to be the causative factor at the lower concentrations of DEP. Nitric oxide reacts with 02'-to produce peroxynitrite (33,34), leading to endothelial cell damage (35). Attenuation of endothelium-dependent relaxation by DEP might, therefore, result from inactivation of EDRF, and/or from inhibition of nitric oxide synthase in endothelial cells by oxygen radicals produced during DEP-incubation.…”

Section: Discussionmentioning

confidence: 99%

Impairment of Endothelium-Dependent Relaxation by Diesel Exhaust Particles in Rat Thoracic Aorta.

et al. 1995

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ABSTRACT-Nitric oxide released from vascular endothelium plays important regulatory roles in cardiovascular and pulmonary systems. Epidemiological studies suggest that diesel exhaust particles (DEP) seem to be one of the causative factors responsible for the recent increase in pulmonary diseases. To clarify the pathogenic mechanism, the effects of DEP on vascular endothelial functions were investigated in terms of endothelium-dependent relaxation. Ring preparations of rat thoracic aorta were preincubated for 10 min with a DEP suspension (1, 10, 100 pg/ml) at 37°C in organ baths and relaxed with cumulative additions of acetylcholine following precontraction with phenylephrine (10-6 M). The relaxation was attenuated by DEP-exposure in a concentration-dependentmanner. An addition of superoxide dismutase (SOD) completely abolished the inhibitory effect of DEP at lower concentrations, but only partially at the higher concentration. DEP (10 tg/ml) neither affected the contractile response to phenylephrine in intact aortic rings nor the endothelium-independent relaxation by sodium nitroprusside in denuded rings, while DEP (100 pg/ml) significantly attenuated both responses. These results suggest that 1) inhaled DEP causes pulmonary inflammation by inhibiting the endothelial formation and/or the effect of nitric oxide and 2) SOD reduces the adverse effects. Keywords: Diesel exhaust particle, Endothelium-dependent relaxation, Thoracic aorta (rat), Superoxide, Acetylcholine Several epidemiological studies indicate that patients with pulmonary diseases such as asthma and chronic bronchitis are increasing in Japan, especially in children living in urban areas. Diesel exhaust contains 2 to 20 times more nitrogen oxides and 30 to 100 times more particles than gasoline exhaust. Moreover, it has been recently reported that diesel exhaust particles (DEP) suspended in phosphate buffer generate superoxide anion radicals (02'-) and hydroxyl radicals ('OH) on incubation at 371C. Sagai et al. suggested that these active oxygen radicals would cause endothelial cell damage leading to pulmonary edema (1). It was reported that reactive oxygens (02'-, 'OH and H202) were causes of pulmonary injury (2) and that 02'-produced from dihydroxyfumarate induced pulmonary endothelial cell damage (3). The earliest stages of histologically observable lung injury occurred in the pulmonary capillary bed (4) and the endothelial cells in capillaries (5). Edward reports that injury of the pulmonary endothelial cells is the pathogenesis of acute lung injury (6). These observations imply that the endothelium plays important protective roles in the development of pulmonary injury.Since the alveolar capillary endothelium lies close to the alveolar epithelium (7), inhaled DEP may easily interact with the endothelium, blood cells and blood components by releasing reactive oxygens and some soluble materials. The endothelium releases numerous biologically important materials, one of which is endothelium-derived relaxing factor (EDRF): nitric oxide (8) or nitrosot...

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Section: Discussionmentioning

confidence: 99%

Impairment of Endothelium-Dependent Relaxation by Diesel Exhaust Particles in Rat Thoracic Aorta.

et al. 1995

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“…SIN-I generates both nitric oxide and superoxide ions 1331. Nitric oxide may react with superoxide to form peroxynitrite (ONOO-) [5], which is unstable at physiological pH, dismutating to form the highly reactive OH' and NO; radicals [73. Removal of superoxide by superoxide dismutase extends the halflife of nitric oxide [34].…”

Section: Discussionmentioning

confidence: 99%

“…Nitric oxide is a small lipophilic molecule, with a halflife of 5-30 s, which is likely to produce cytotoxic, mutagenic or second messenger effects in the cell in which it is produced, or in adjacent cells. It reacts rapidly with oxygen and oxygen radicals [4] to give rise to other species, such as peroxynitrite (ONOO-) [5], (with a halflife l-2 s) which are also thought to exert damaging effects [6]. Conditions favouring formation of peroxynitrite have recently been associated with neurotoxicity, whereas a change in the ambient redox state can result in a paradoxical neuroprotective effect of nitric oxide [71.…”

Section: Introductionmentioning

confidence: 99%

Endogenous nitric oxide induced by interleukin‐1β in rat islets of Langerhans and HIT‐T15 cells causes significant DNA damage as measured by the ‘comet’ assay

et al. 1993

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We have used the comet assay (single cell gel electrophoresis) to measure nitric oxide-induced DNA damage in rat islets of Langerhans and insulin-containing HIT-T15 cells. Damage was induced following treatment with the nitric oxide donor SIN-l, which also releases superoxide, but was not reduced by exogenous superoxide dismutase, suggesting that nitric oxide itself, rather than superoxide or peroxynitrite may be the active species. The DNA damaging effect of nitric oxide was easily detectable at the earliest time point tested (15 min). Damage also resulted following induction of nitric oxide synthase by the cytokine interleukin-I/? in both islets and HIT-T15 cells and was prevented by replacing the substrate, arginine, with nitromonomethyl arginine. Thus intracellular levels of nitric oxide generated by interleukin-l/l-induced nitric oxide synthase were sufficient to cause DNA damage in islet cells and HIT-T15 cells.

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“…NO reacts rapidly with superoxide forming peroxynitrite anion (Blough and Zafiriou, 1985;McCall et al, 1989) and this can result in superoxide detoxification (Wink et al, 2001). This element may contribute to the observed tendency of an increased resistance to PDT of tumours characterised by elevated intrinsic NO production (Korbelik et al, 2000).…”

Section: Donovanmentioning

confidence: 99%

Ischaemia-reperfusion injury in photodynamic therapy-treated mouse tumours

2003

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Prompted by the observation of ischaemia development during the treatment of tumours by photodynamic therapy (PDT) that is typically followed by a restoration of tumour blood flow and by the indications of secondary superoxide generation after PDT, we aimed in this study to obtain evidence of the induction of ischaemia-reperfusion (I/R) injury in PDT-treated tumours. Using subcutaneous mouse FsaR fibrosarcoma model and Photofrin-based PDT treatment, we have examined the activity of xanthine oxidase (XO, a key enzyme in the I/R injury development) in tumours before and after the therapy. Compared to the levels in nontreated tumours, there was a five-fold increase in the activity of this enzyme in tumours excised immediately after PDT. This burst of elevated XO activity declined rapidly, returning to the pretreatment levels within the next 30 min. Visible reflectance spectroscopy confirmed the occurrence of a PDT-induced strong but temporary reduction in tumour oxygenation. The administration of XO inhibitor oxypurinol prevented this PDT-induced rise in XO activity. The oxypurinol treatment also decreased the extent of neutrophil accumulation in PDT-treated tumours and reduced the level of PDT-mediated cures. These results demonstrate the induction of I/R injury in PDT-treated tumours, and show that it can contribute to the therapy outcome. Since I/R injury is a wellrecognised proinflammatory insult, we suggest that its induction in PDT-treated tumours promotes the development of inflammatory response that has become established as a key element of the antitumour effect of PDT.

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Reaction of superoxide with nitric oxide to form peroxonitrite in alkaline aqueous solution

Cited by 515 publications

References 0 publications

Impairment of Endothelium-Dependent Relaxation by Diesel Exhaust Particles in Rat Thoracic Aorta.

Impairment of Endothelium-Dependent Relaxation by Diesel Exhaust Particles in Rat Thoracic Aorta.

Endogenous nitric oxide induced by interleukin‐1β in rat islets of Langerhans and HIT‐T15 cells causes significant DNA damage as measured by the ‘comet’ assay

Ischaemia-reperfusion injury in photodynamic therapy-treated mouse tumours

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