Oxidative Potential Versus Biological Effects: A Review on the Relevance of Cell-Free/Abiotic Assays as Predictors of Toxicity from Airborne Particulate Matter

Johan Øvrevik

doi:10.3390/ijms20194772

Abstract

Background and Objectives: The oxidative potential (OP) of particulate matter (PM) in cell-free/abiotic systems have been suggested as a possible measure of their biological reactivity and a relevant exposure metric for ambient air PM in epidemiological studies. The present review examined whether the OP of particles correlate with their biological effects, to determine the relevance of these cell-free assays as predictors of particle toxicity. Methods: PubMed, Google Scholar and Web of Science databases were searched to identify relevant studies published up to May 2019. The main inclusion criteria used for the selection of studies were that they should contain (1) multiple PM types or samples, (2) assessment of oxidative potential in cell-free systems and (3) assessment of biological effects in cells, animals or humans. Results: In total, 50 independent studies were identified assessing both OP and biological effects of ambient air PM or combustion particles such as diesel exhaust and wood smoke particles: 32 in vitro or in vivo studies exploring effects in cells or animals, and 18 clinical or epidemiological studies exploring effects in humans. Of these, 29 studies assessed the association between OP and biological effects by statistical analysis: 10 studies reported that at least one OP measure was statistically significantly associated with all endpoints examined, 12 studies reported that at least one OP measure was significantly associated with at least one effect outcome, while seven studies reported no significant correlation/association between any OP measures and any biological effects. The overall assessment revealed considerable variability in reported association between individual OP assays and specific outcomes, but evidence of positive association between intracellular ROS, oxidative damage and antioxidant response in vitro, and between OP assessed by the dithiothreitol (DDT) assay and asthma/wheeze in humans. There was little support for consistent association between OP and any other outcome assessed, either due to repeated lack of statistical association, variability in reported findings or limited numbers of available studies. Conclusions: Current assays for OP in cell-free/abiotic systems appear to have limited value in predicting PM toxicity. Clarifying the underlying causes may be important for further advancement in the field.

Highlights

Airborne particulate matter (PM) represents one of the major environmental risk factors for disease and premature death worldwide, and has been associated with development or exacerbation of a number of adverse health effects including asthma, chronic obstructive pulmonary disease (COPD), cancer, cardiovascular disease (CVD), metabolic and neurological disorders and adverse birth effects [1,2,3,4,5,6]
The purpose of this paper was to review to what extent oxidative potential (OP) in cell-free/abiotic systems provides a relevant measure of PM-toxicity, correlating with the biological effects observed in PM-exposed cells, animals and humans
Statistical significant associations between OP and biological effects were reported in 22 of the 29 independent studies were statistical analysis were applied [29,32,43,44,49,52,57,58,59,60,63,65,66,74,75,76,77,78,79,80,81,82,83,84]: 10 independent studies reported that at least one OP measure was statistically significantly associated with all endpoints examined [43,49,52,57,63,66,78,79,80,81,83], while additional 12 independent studies reported that at least one OP measure was significantly associated with at least one effect outcome [29,32,44,58,59,60,65,74,75,76,77,82,84]

Summary

Introduction

Airborne particulate matter (PM) represents one of the major environmental risk factors for disease and premature death worldwide, and has been associated with development or exacerbation of a number of adverse health effects including asthma, chronic obstructive pulmonary disease (COPD), cancer, cardiovascular disease (CVD), metabolic and neurological disorders and adverse birth effects [1,2,3,4,5,6]. Non-oxidant mediated mechanisms of PM-toxicity are well known [9], the concept of OP as determinant for PM-toxicity has received considerable attention and it has been linked to all fields of particle toxicology and all the main outcomes of particle exposure, as extensively reviewed by others [14,15,16,17,18,19]. The oxidative potential (OP) of particulate matter (PM) in cell-free/abiotic systems have been suggested as a possible measure of their biological reactivity and a relevant exposure metric for ambient air PM in epidemiological studies. The present review examined whether the OP of particles correlate with their biological effects, to determine the relevance of these cell-free assays as predictors of particle toxicity. Clarifying the underlying causes may be important for further advancement in the field

Objectives

Results

Conclusion