Background-Cigarette smoking is a well-known risk factor for the development of cardiovascular disease, yet the mechanism of action involved is not completely understood. Because cigarette smoke contains superoxide and other reactive oxygen species, it has been hypothesized that some of the adverse effects of smoking may result from oxidative damage to endothelial cells, which results in nitric oxide (NO) shortage. However, little information is available regarding the acute effects of smoking on plasma concentrations of NO and antioxidants. We measured the changes in the combined plasma concentrations of nitrate and nitrite as an index of NO concentration, as well as changes in concentrations of major serum antioxidants (ascorbic acid, cysteine, methionine, and uric acid) in smokers after smoking a single cigarette. Methods and Results-A randomized crossover study of the effects of smoking a single cigarette was performed in 20 smokers. Smoking a sham cigarette induced no significant changes in all assayed parameters. However, smoking a single cigarette significantly decreased nitrate and nitrite plasma concentrations by 3.5Ϯ1.2 and 3.4Ϯ1.1 mol/L, compared with plasma concentrations at presmoking and sham smoking, respectively. The concentrations of ascorbic acid and other antioxidants were also significantly lower after smoking a single cigarette. These parameters returned to preexperimental levels 60 minutes after smoking cessation. Conclusion-The present findings indicate that smoking a single cigarette temporarily decreases nitrate, nitrite, and serum antioxidant concentrations in the plasma. These transient changes may partially contribute to coronary vasoconstriction, which is routinely observed after smoking.

Phthalate esters have been used extensively as plasticizers of synthetic polymers. Recent studies have revealed that these esters induce atrophy of the testis, although its pathogenesis remains unknown. The present study describes the possible involvement of oxidative stress in the pathogenesis of atrophy of the rat testis induced by di(2-ethylhexyl)phthalate (DEHP). Biochemical and immunohistochemical analysis revealed that oral administration of DEHP increased the generation of reactive oxygen species, with concomitant decrease in the concentration of glutathione and ascorbic acid in the testis, and selectively induced apoptosis of spermatocytes, thereby causing atrophy of this organ. Oxidative stress was selectively induced in germ cells, but not in Sertoli cells, treated with mono(2-ethylhexyl)phthalate (MEHP), a hydrolysed metabolite of DEHP. Furthermore, MEHP selectively induced the release of cytochrome c from mitochondria of the testis. These results indicate that oxidative stress elicited by MEHP principally injured mitochondrial function and induced the release of cytochrome c, thereby inducing apoptosis of spermatocytes and causing atrophy of the testis.

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The results demonstrate a critical role of SOD2 in protection against oxidative challenge. Cells from HET mice showed greater apoptotic cell death, whereas in those from HEMI mice, cell death induced by oxidative injury was suppressed.

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Although S-nitrosoglutathione (GS-NO) and other S-nitrosothiols (RS-NO) exhibit activity attributable to nitric oxide (NO), the dynamic aspects of their metabolism remain to be elucidated. To determine the fates and functions of RS-NO, the stability of GS-NO was analyzed in plasma, and various fractions of liver and kidney. GS-NO was fairly stable under physiological conditions in plasma and buffer solutions. However, GS-NO was rapidly decomposed in the presence of either homogenates of rat liver and kidney or their supernatant fractions. The ability of the supernatants to decompose GS-NO remained unchanged after the removal of proteins and large molecular weight compounds. Physiological levels of reducing agents, such as reduced glutathione (GSH), ascorbic acid (AsA), and cysteine, also enhanced the decomposition of RS-NO; the order of their potency was AsA > cysteine >GSH. Considering their intra-cellular concentrations and potency, AsA might principally be responsible for the enhanced decomposition of GS-NO. NO, GS-NO, and related RS-NO inhibited the respiration of Ehrlich ascites tumor cells. The inhibitory effect of GS-NO was enhanced by the reducing agents (cysteine>AsA>GSH). Intravenously administered GS-NO exhibited a depressor action through some ascorbic acid enhancable mechanism. Thus, the metabolism and biological function of GS-NO and related RS-NO might be affected by AsA and other reducing agents.

We previously reported that irradiation of titanium dioxide (TiO2) in ethanol generates both singlet oxygen (1O2) and superoxide anion (O2*-) as measured by EPR spectroscopy. The present study describes the production of reactive oxygen species upon irradiation of TiO2 in aqueous suspension as determined by EPR spectroscopy using 2,2,6,6-tetramethyl-4-piperidone (4-oxo-TMP) and 5,5-dimethyl-pyrroline-N-oxide (DMPO). Photoproduction of 1O2 by suspended TiO2, detected as 2,2,6,6-tetramethyl-4-piperidone-N-oxyl (4-oxo-TEMPO), was measured in water and deuterium oxide (D2O) in the presence or absence of sodium azide (NaN3) and under air or argon atmospheres. Production of a DMPO-OH adduct was examined in 4-oxo-TMP containing medium in the presence or absence of dimethyl sulfoxide (DMSO). The signal for the DMPO spin adduct of superoxide anion was not observed in aqueous conditions. Kinetic analysis revealed that 1O2 was produced at the surface of irradiated TiO2 in aqueous suspension as was observed in ethanol. Kinetic analysis revealed that the formation of DMPO-OH adduct reflects oxidation of DMPO by 1O2 rather than the trapping of the hydroxyl radical produced by the reaction of photo-exited TiO2 and water. The production of large amounts of 1O2 by TiO2 in aqueous suspension as compared to those in ethanol and possible formation of hydroxyl radical in aqueous suspension but not in alcohol, suggest that irradiation of TiO2 in aqueous environments is biologically more important than that in non-aqueous media.