Oxidative Injury in The Lungs of Neonatal Rats Following Short-Term Exposure to Ultrafine Iron and Soot Particles

Abstract

Greater risk of adverse effects from particulate matter (PM) has been noted in susceptible subpopulations, such as children. However, the physicochemical components responsible for these biological effects are not understood. As critical constituents of PM, transition metals were postulated to be involved in a number of pathological processes of the respiratory system through free radical-medicated damage. The purpose of this study was to examine whether oxidative injury in the lungs of neonatal rats could be induced by repeated short-term exposure to iron (Fe) and soot particles. Sprague Dawley rats 10 d of age were exposed by inhalation to two different concentrations of ultrafine iron particles (30 or 100 µg/m³) in combination with soot particles adjusted to maintain a total particle concentration of 250 µg/m³. Exposure at 10 d and again at 23 d of age was for 6 h/d for 3 d. Oxidative stress was observed at both Fe concentrations in the form of significant elevations in glutathione disulfide (GSSG) and GSSG/glutathione (GSH) ratio and a reduction in ferric/reducing antioxidant power in bronchoalveolar lavage. A significant decrease in cell viability associated with significant increases in lactate dehydrogenase (LDH) activity, interleukin-1-beta (IL-1β), and ferritin expression was noted following exposure to particles containing the highest Fe concentration. Iron from these particles was shown to be bioavailable in an in vitro assay using the physiologically relevant chelator, citrate. Data indicate that combined Fe and soot particle exposure induces oxidative injury, cytotoxicity and pro-inflammatory responses in the lungs of neonatal rats.

Cai-Yun Zhong and Ya-Mei Zhou contributed equally to this work.

The authors appreciate Dr. Suzette Smiley-Jewell for her editorial assistance in the preparation of this article. This work was supported by grants from the Health Effects Institute, U.S. Environmental Protection Agency (R82915 and R832414), National Institutes of Health (5R01ES012957), and National Institute for Occupational Safety and Health (OH07550). The preliminary observations for portions of this research were reported in a limited-distribution final report to the Health Effects Institute (Pinkerton et al., 2008).