Citation:

Stevens, J., D. DeMarini, M. Hazari, D. Hunter, S. Padilla, AND A. Farraj. Zebrafish Locomotor Responses Demonstrate Irritant Effects of Fine Particulate Matter Sources and a Role for TRPA1. Society of Toxicology, New Orleans, LA, March 13 - 17, 2016.

Impact/Purpose:

The research findings demonstrate the utility of a simple and rapid assay in zebrafish to assess irritant effects of air pollution-derived particulate matter. Because health effects of PM stem in part from the irritating properties of PM components and zebrafish responses to irritants take place through similar mechanisms to those in mammals, this zebrafish model may be useful in assessment of the relative toxicity of PM sources. In addition, mechanistic investigations can be easily carried out, with current study findings pointing to a key mechanism (i.e. TRPA1) that has relevance to mammalian modes of toxicity and disease. This approach may expedite comparative toxicity assessments and thus hazard determinations of PM, facilitate identification of the most toxic PM sources and causal components, and identify putative modes of action.

Description:

Fine particulate matter (PM) air pollution is a complex mixture of chemicals, the composition of which is determined by contributing sources, and has been linked to cardiopulmonary dysfunction. These effects stem in part from the irritating properties of PM constituents, which often elicit pain and inflammatory responses via activation of the chemosensing transient receptor potential (TRP) cation channel TRPA1. Zebrafish larvae sense a variety of chemical stimuli, the behavioral responses to which can be easily measured in routine assays. The purpose of this study was to examine the utility of the zebrafish as a sentinel species to assess PM sources for their capacity to trigger irritant responses. We hypothesized that exposure of zebrafish embryos to an organic fraction of diesel exhaust particulate matter (DEP), a PM rich in pro-oxidant polyaromatic hydrocarbons, would elicit concentration-dependent irritant responses. In addition, given that zebrafish express TRPA1 on their skin, we hypothesized that the DEP-induced irritant responses in zebrafish would be mediated by activation of TRPA1. Six day-old zebrafish (n=24/experimental condition) were acutely exposed to DEP (8 to 40 µg/ml) and activity was assessed in the dark at 26.0°C for 30 minutes using video tracking software. Activity was also measured in DEP-exposed (28 µg/ml) fish pretreated with a TRPA1 antagonist (HC 030031, 50 µM). Acute DEP exposure caused marked concentration-dependent hyperactivity. Furthermore, pretreatment with the TRPA1 antagonist blocked the DEP-induced hyperactivity response. Taken together, the dynamic range of the assay and the mediation of responses by mechanisms analogous to those in mammals support zebrafish as a useful model to assess PM sources for their ability to elicit irritant-responses (This abstract does not reflect US EPA policy).

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