Lung Permeability, Antioxidant Status, and NO₂Inhalation: A Selenium Supplementation Study in Rats∗

Abstract

Little is known about antioxidant status, selenium status in particular, and lung response to NO2, which acts as a proinflammatory air pollutant. The effects of a low selenium diet (1.3 microg Se/d) with or without selenium supplementation were therefore studied in 128 Wistar rats, 2 mo old, male exposed to either acute (50 ppm, 30 min), intermittent subacute (5 ppm, 6 h/d, 5 d), intermittent long-term NO2 (1 ppm, 10 ppm, 6 h/d, 5 d/wk, 28 d), or normal atmospheric air (controls). Following sacrifice, measurements of lipid peroxidation (thiobarbituric acid-reactive substances, chemiluminescence), antioxidative protective enzymes (glutathione peroxidase [GPx], superoxide dismutase [SOD], glutathione S-transferase [GST], ceruloplasmin), lung damage (lactate dehydrogenase, alkaline and acid phosphatases), lung permeability (total protein, albumin), and inflammation (cell populations), along with the determination of new biomarkers such as CC16 (Clara-cell protein), were performed in serum and bronchoalveolar lavage fluid (BALF). While selenium-supplemented animals had increased GPx activity in serum prior to inhalation experiments, they also had decreased BALF CC16, blood SOD, and GST levels. Nevertheless, the protective role of normal selenium status with respect to NO2 lung toxicity was evident both for long-term and acute exposures, as the increase in BALF total proteins and corresponding decrease in serum (indicating increased lung permeability) was significantly more pronounced in selenium-deficient animals. During the various inhalation experiments, serum CC16 demonstrated its key role as an early marker of increased lung permeability. These findings corroborate the important role of selenium status in NO2 oxidative damage modulation, but also indicate, in view of its negative impact on CC16, a natural anti-inflammatory and immunosuppressor, that caution should be used prior to advocating selenium supplementation.

Oxidants and the pathogenesis of lung diseases

“…If not quenched, this reaction can permanently damage cell membranes, ultimately leading to cell death. Exposures to oxidant air pollutants cause lipid peroxidation in humans and rodents 15–19. Furthermore, the end products of lipid peroxidation can lead to subsequent pathological consequences.…”

Long-term exposure to traffic-related air pollution and stroke: A systematic review and meta-analysis

“…Also a better understanding of the molecular and cellular actions of nitrogen oxides on the cardiometabolic system is necessary to provide mechanistic evidence for a plausible adverse health effect. So far, only limited evidence is available from toxicological studies at relevant ambient concentrations (Burbure et al, 2007;Channell et al, 2012;Huang et al, 2012;Li et al, 2011;Riedl et al, 2012).…”