Nitric Oxide Generation in Aqueous Solutions of Cigarette Smoke and Approaches to Its Origin

Abstract

By using the ESR spin trapping technique with the N-methyl-D-glucamine dithiocarbamate (MGD)2-Fe(II) complex, the generation of nitric oxide (NO), a gaseous free radical, was observed in NO spin trapping solution bubbled with the filtered main-stream of cigarette smoke. The ESR signal with a three-line spectrum characteristic of an NO radical, which was not observed immediately after bubbling of smoke, started rapidly increasing with time up to around 25 min after the last addition of ferrous ions Fe(II), and then slowly approached a peak value dependent on the burned cigarette mass and on the smoking speed. The production of NO was, however, much affected by air oxidation and enhanced by the addition of ascorbic acid. A certain concentration of sodium nitrite (NaNO2) solution, in which nitrite NO2- is assumed as the main origin of the NO, mimicked closely the time course of NO generation resulting from the smoke of one cigarette. The cigarette smoke that was passed through alkaline pyrogallol solution as a deoxidizer; however, it exhibited an unchanged intensity of NO signal throughout the measurement. These results strongly suggest that NO would be gradually reproduced from NO2- in the reductive aqueous solution containing excess Fe(II) through NO2, which is initially formed and is concomitantly oxidized from NO in cigarette smoke.

Electron paramagnetic resonance investigation of the free radicals in the gas and particulate phases of cigarette smoke using spin-trapping techniques

“…2 Despite their reactivity, free radicals have been detected in the vapor phase of cigarette smoke for as long as 5 minutes after combustion. [6][7][8][9][10] This result is due to two specific characteristics of cigarette smoke:…”

“…They include direct EPR (flow) detection, indirect EPR of spin-trapped species, short-lived radical and stable radical coupling followed by HPLC, LC, fluorescence, GC, MS, or IR methods. [3][4][5][6][7][8][9][10][11] It can be argued that EPR spectroscopy provides the most information about free radicals in a 'single' experiment. This is because the EPR technique is specific (it detects only unpaired electrons), highly sensitive (it can detect free radicals at less than 10 -10 M) and in many cases may give some structural information such as the nature of the atoms closest to the unpaired electron.…”

“…[6][7][8][9][10][11][12] To enable detection, these are reacted with a diamagnetic molecule, called a spin-trap, in order to form a persistent spin-adduct. This increases the lifetime to minutes-hours, which allows the radical to be seen easily and identified by EPR spectroscopy (Scheme 2).…”

“…8 The hybrid compound (DPPH-PBN, Figure 1) contains a stable free radical moiety of the hydrazyl type and a nitrone spin-trap moiety, which allows it to be used as a sensor to probe free radical chemistry. 14 In this experiment, the objective was to identify only the O-centered radicals (as a mixture of alkoxyl and peroxyl radicals).…”

Regulation of Nitric Oxide by Cigarette Smoke in Airway Cells

“…Smoking decreases exhaled NO levels, but the mechanism is unknown. The possible pathways include: 1) cigarette smoking increases ADMA levels, thus suppressing NO production; 2) cigarette smoking could increase NO x levels via the oxidative stress pathway which in turn inhibits NO production by negative feedback; 3) cigarette smoking could increase NO x levels directly in EBC by donating oxides of nitrogen such as NO 2 · and NO 3 ·, and again these inhibit NO production by negative feedback [24,28]. To explore the mechanism behind the cigarette smoking altering NO metabolism, this in vitro study was conducted.…”