Particle-induced Oxidative Stress Research Articles

Source-Dependent Variation in Hydroxyl Radical Production by Airborne Particulate Matter

Epidemiological studies suggest exposure to airborne particles is responsible for a wide range of adverse health effects, potentially arising from particle-induced oxidative stress. A highly sensitive fluorescence method was employed to measure the production of hydroxyl radical by a broad range of particle types including urban dust, diesel particulate matter, coal fly ash, kaolinite, and silica. Little or no production of *OH was observed in the absence of an added electron donor or H202. In the presence of a biological electron donor (NADPH, 3 mM), the rate of *OH production (ROH) for 3 mg/mL of these particles varied from 23 nM s(-1) for diesel particulate matter (SRM 2975) to 0.20 nM s(-1) for coal fly ash (SRM 2689). No detectable *OH was produced by kaolinite or silica. Hydroxyl radical formation was eliminated under anaerobic conditions and in the presence of catalase, indicating that 02 and H202 are required for its generation. Partial inhibition of *OH formation by superoxide dismutase (SOD) was also observed in some cases, suggesting that superoxide (O2*-) is also involved. The metal chelator deferoxamine mesylate (DFX) in most cases suppressed *OH formation, but diethylenetriaminepentaacetic acid (DTPA) generally enhanced it, implicating metal ion reactions in OH generation as well. The dependence of ROH on NADPH concentration further implicates particle surface reactions in *OH formation. To our knowledge, these measurements provide the first quantitative estimate of ROH for a broad range of particle types.

Oxymetazoline Inhibits Proinflammatory Reactions: Effect on Arachidonic Acid-Derived Metabolites

The nasal decongestant oxymetazoline effectively reduces rhinitis symptoms. We hypothesized that oxymetazoline affects arachidonic acid-derived metabolites concerning inflammatory and oxidative stress-dependent reactions. The ability of oxymetazoline to model pro- and anti-inflammatory and oxidative stress responses was evaluated in cell-free systems, including 5-lipoxygenase (5-LO) as proinflammatory, 15-lipoxygenase (15-LO) as anti-inflammatory enzymes, and oxidation of methionine by agglomerates of ultrafine carbon particles (UCPs), indicating oxidative stress. In a cellular approach using canine alveolar macrophages (AMs), the impact of oxymetazoline on phospholipase A(2) (PLA(2)) activity, respiratory burst and synthesis of prostaglandin E(2) (PGE(2)), 15(S)-hydroxy-eicosatetraenoic acid (15-HETE), leukotriene B(4) (LTB(4)), and 8-isoprostane was measured in the absence and presence of UCP or opsonized zymosan as particulate stimulants. In cell-free systems, oxymetazoline (0.4-1 mM) inhibited 5-LO but not 15-LO activity and did not alter UCP-induced oxidation of methionine. In AMs, oxymetazoline induced PLA(2) activity and 15-HETE at 1 mM, enhanced PGE(2) at 0.1 mM, strongly inhibited LTB(4) and respiratory burst at 0.4/0.1 mM (p < 0.05), but did not affect 8-isoprostane formation. In contrast, oxymetazoline did not alter UCP-induced PLA(2) activity and PGE(2) and 15-HETE formation in AMs but inhibited UCP-induced LTB(4) formation and respiratory burst at 0.1 mM and 8-isoprostane formation at 0.001 mM (p < 0.05). In opsonized zymosan-stimulated AMs, oxymetazoline inhibited LTB(4) formation and respiratory burst at 0.1 mM (p < 0.05). In conclusion, in canine AMs, oxymetazoline suppressed proinflammatory reactions including 5-LO activity, LTB(4) formation, and respiratory burst and prevented particle-induced oxidative stress, whereas PLA(2) activity and synthesis of immune-modulating PGE(2) and 15-HETE were not affected.

Seasonal Variations in Air Pollution Particle-Induced Inflammatory Mediator Release and Oxidative Stress

Health effects associated with particulate matter (PM) show seasonal variations. We hypothesized that these heterogeneous effects may be attributed partly to the differences in the elemental composition of PM. Normal human bronchial epithelial (NHBE) cells and alveolar macrophages (AMs) were exposed to equal mass of coarse [PM with aerodynamic diameter of 2.5–10 μm (PM2.5–10)], fine (PM2.5), and ultrafine (PM < 0.1) ambient PM from Chapel Hill, North Carolina, during October 2001 (fall) and January (winter), April (spring), and July (summer) 2002. Production of interleukin (IL)-8, IL-6, and reactive oxygen species (ROS) was measured. Coarse PM was more potent in inducing cytokines, but not ROSs, than was fine or ultrafine PM. In AMs, the October coarse PM was the most potent stimulator for IL-6 release, whereas the July PM consistently stimulated the highest ROS production measured by dichlorofluorescein acetate and dihydrorhodamine 123 (DHR). In NHBE cells, the January and the October PM were consistently the strongest stimulators for IL-8 and ROS, respectively. The July PM increased only ROS measured by DHR. PM had minimal effects on chemiluminescence. Principal-component analysis on elemental constituents of PM of all size fractions identified two factors, Cr/Al/Si/Ti/Fe/Cu and Zn/As/V/Ni/Pb/Se, with only the first factor correlating with IL-6/IL-8 release. Among the elements in the first factor, Fe and Si correlated with IL-6 release, whereas Cr correlated with IL-8 release. These positive correlations were confirmed in additional experiments with PM from all 12 months. These results indicate that elemental constituents of PM may in part account for the seasonal variations in PM-induced adverse health effects related to lung inflammation.

Alzheimer's Disease: a Pathogenic Role for Aluminosilicate-Induced Phagocytic Free Radicals

The occurrence of aluminosilicate deposits within the cerebral plaques in Alzheimer's senile dementia sufferers has prompted further consideration of the possible role of such materials in the aetiology and pathogenesis of the disease. We have monitored the ability of various natural and synthetic model aluminosilicate particulates of differing morphological and chemical composition to stimulate the generation of phagocyte-derived free radical reactive oxygen metabolites (ROM) using an in vitro chemiluminescent technique on purified human blood-derived polymorphonuclear leukocytes (PMN). The results indicate that an enhanced chemiluminescent response is produced by calcium-bearing fibriform particulates. It is proposed that an analogous in vivo particle-induced and phagocyte-mediated oxidative stress could provide a potential pathogenic mechanism in the development of Alzheimer's disease.

Discharge pattern of single motor units in basal ganglia disorders.

We studied the discharge pattern of motor units (MUs) from the first dorsal interosseous muscle during slight stationary isometric contraction. In six controls, seven patients with parkinsonism, and five patients with choreic disorders, we analyzed 78 MUs. About one-half of the MUs in both patient groups fired irregularly as shown by interval histograms, joint interval histograms, and corresponding statistical calculations. Cross-correlation techniques revealed a characteristic type of MU synchronization in parkinsonism. Analysis of the MU discharge pattern can be useful in clinical assessment of these disorders.