Impacts of antioxidants on hydroxyl radical production from individual and mixed transition metals in a surrogate lung fluid

Abstract

Inhalation of ambient particulate matter causes morbidity and mortality in humans. One hypothesized mechanism of toxicity is the particle-induced formation of reactive oxygen species (ROS) – including the highly damaging hydroxyl radical (·OH) – followed by inflammation and a variety of diseases. While past studies have found correlations between ROS formation and a variety of metals, there are no quantitative measurements of ·OH formation from transition metals at concentrations relevant to 24-hour ambient particulate exposure. This research reports specific and quantitative measurements of ·OH formation from 10 individual transition metals (and several mixtures) in a cell-free surrogate lung fluid (SLF) with four antioxidants: ascorbate, citrate, glutathione, and uric acid. We find that Fe and Cu can produce ·OH under all antioxidant conditions as long as ascorbate is present and that mixtures of the two metals synergistically increase ·OH production. Manganese and vanadium can also produce ·OH under some conditions, but given that their ambient levels are typically very low, these metals are not likely to chemically produce significant levels of ·OH in the lung fluid. Cobalt, chromium, nickel, zinc, lead, and cadmium do not produce ·OH under any of our experimental conditions. The antioxidant composition of our SLF significantly affects ·OH production from Fe and Cu: ascorbate is required for ·OH formation, citrate increases ·OH production from Fe, and both citrate and glutathione suppress ·OH production from Cu. MINTEQ ligand speciation modeling indicates that citrate and glutathione affect ·OH production by changing metal speciation, altering the reactivity of the metals. In the most realistic SLF (i.e., with all four antioxidants), Fe generates approximately six times more ·OH than does the equivalent amount of Cu. Since levels of soluble Fe in PM are typically higher than those of Cu, our results suggest that Fe dominates the chemical generation of ·OH from deposited particles in the lungs.

Quantification of environmentally persistent free radicals and reactive oxygen species in atmospheric aerosol particles

“…Previous studies have shown that redox-active components such as transition metals and quinones can induce ROS formation in surrogate lung lining fluid upon interactions with antioxidants (Charrier and Anastasio, 2011;Charrier et al, 2014). This study also implies that ROS can be formed in lung lining fluid upon inhalation and respiratory deposition of atmospheric aerosol particles.…”

Heavy Metal Compositions and Bioreactivity of Airborne PM10 in a Valley-Shaped City in Northwestern China

“…Fe is often linked to the oxidative damage caused by particles (Valavanidis et al, 2000;Han et al, 2001;See et al, 2007;Di Pietro et al, 2009;Charrier and Anastasio, 2011), and soluble Fe affects oxidative capacity through (Shi et al, 2003;Risom et al, 2005;Vidrio et al, 2008;Nawrot et al, 2009). The ICP-MS analysis indicated that, although total Fe concentration in the Lanzhou PM 10 samples was much higher than that in the soluble fraction, the concentration of soluble Fe was significant, reaching as much as 1105 μg/g.…”

A rapid assessment of the impact of hazard reduction burning around Sydney, May 2016

“…However, in very small (ultrafine) size ranges, these particles have been linked with significant oxidative stress mediated toxicity (Duffin, Mills & Donaldson, 2007). Some metals, such as zinc oxide, will dissolve in the body (Gilmour et al, 2006;Charrier & Anastasio, 2011). Zinc ions have many physiological functions, but they can also interfere with the body's homeostasis, leading to such adverse effects as oxidative stress and inflammation.…”