Investigating the Source of Particulate Matter Toxicity: Kinetics of Reactive Oxygen Species from Biomass Burning Components in Lung Lining Fluids and Characterization of Toxic Components
Epidemiological studies have shown that inhalation of particulate matter (PM) is associated with increased cardiovascular diseases, respiratory diseases, asthma and cancer. However, the underlying biological mechanisms and PM components responsible for adverse health outcomes are poorly understood. Induction of oxidative stress mediated by an overproduction of reactive oxygen species (ROS) is one hypothesis for PM induced health effects. The PM components responsible for ROS generation and under conditions relevant to the lung are not well known. Inhalation of PM containing of water-soluble like substances (HULIS) are thought to disrupt cellular iron homeostasis, contributing to the development of pulmonary inflammation and disease. Cigarette smoke and wood smoke contain significant amounts of HULIS, but there is scant literature characterizing HULIS in these particles. Malondialdehyde (MDA) is a toxic aldehyde traditionally measured in biological systems as a marker for oxidative stress. Interestingly, a handful of literature suggests that MDA may be present in ambient PM, potentially adding to the toxicity of inhaled PM. However, no study has quantified MDA in ambient PM.
In this work we apply the terephthalate probe, thermodynamic modeling and chemical kinetics modeling to elucidate mechanisms of OH generation from HULIS-Fe interactions in simulated lung fluids (SLF) and human bronchoalveolar lavage fluids (BALF). We employ fluorescence and infrared spectroscopy to characterize HULIS isolated from the water-soluble fraction of cigarette smoke condensate and wood smoke particles. We apply the 2-thiobarbituric acid method on biomass burning and urban PM2.5 to quantify ambient particle phase MDA for the first time.
We use Suwannee River Fulvic Acid (SRFA) as a surrogate for HULIS and investigate its impact on OH generation from Fe(II) in SLF and BALF. Model and experimental results are used to find best-fit rate coefficients for key reactions. In SLF, modeling results indicate SRFA strongly chelates Fe species and enhances Fe-mediated reduction of O2 to O2- to 5.1 � 1.5 M-1 s-1 and destruction of H2O2 to (4.3 � 1.4) � 103 M-1 s-1. In BALF, the dominant Fe binding protein is albumin but the impact of albumin-Fe complexes on ROS generation has never been defined. Using a rate limiting approximation and experiments measuring OH generation, we estimate that the rate constant for albumin-Fe mediated O2 to O2- reduction is (1.8 � 0.1) M-1 s-1. We also estimate the rate constant for SRFA-Fe(II) mediated O2 to O2- reduction to be 2.7 � 0.3 M-1 s-1.
Fluorescence and Fourier transform infrared (FTIR) spectroscopy is used on HULIS isolated from cigarette smoke condensate and wood smoke particles. Fluorescence spectra indicate that HULIS in both cigarette smoke condensate and wood smoke contains fluorophores that closely resemble those of SRFA. FTIR spectroscopy further indicates that isolated HULIS contain similar organic functional groups as SRFA, but with higher aliphatic, ether, primary alcohol, organonitrogen character. Using the 2-thiobarbiutric acid assay, we estimate ambient malondialdehyde concentrations to be 40.7 ng/m3 – 75.3 ng/m3 in biomass burning and urban PM2.5 extracts, making up an average of (1.37 � 0.12) �10-2 % of total PM2.5 mass. These concentrations are comparable to previous field measurements of particle phase methylglyoxal and malonic acid, two similar atmospheric carbonyls.