# Ozone Aggravated the Toxicity of Fine Particulate Matter by Impairing Membrane Stability and Facilitating Particle Internalization

## TL;DR

Ozone increases the harmful effects of fine particulate matter by damaging cell membranes and DNA, but astaxanthin can help reduce these effects.

## Contribution

O3 enhances PM2.5 toxicity through membrane damage and DNA breaks, with AST as a potential therapeutic.

## Key findings

- O3 exposure increases PM2.5-induced DNA double-strand breaks.
- O3 disrupts membrane integrity, leading to higher PM2.5 accumulation in cells.
- Astaxanthin reduces the adverse effects of PM2.5 and O3 co-exposure.

## Abstract

The combined pollution of fine particulate matter (PM2.5) and ozone (O3) is increasing synergistically on a global scale, posing a serious threat to human health. However, the joint toxicity and the underlying mechanisms associated with co-exposure to PM2.5 and O3 remain poorly understood. Through complementary in vivo animal models and in vitro cellular assays, the results demonstrate that although there was no synergistic cytotoxicity effect between PM2.5 and O3, the presence of O3 significantly enhanced the genotoxicity of PM2.5 by inducing severe DNA double-strand breaks. Furthermore, O3 exposure significantly exacerbated the bioaccumulation of PM2.5 by disturbing the cellular membrane integrity, thus leading to synergistic toxicity in bronchial cells and mouse lungs. Astaxanthin (AST) effectively antagonized the adverse effects of PM2.5 and O3 co-exposure by maintaining cell membrane integrity. These findings enhance our understanding of the pathophysiological mechanisms induced by co-exposure to PM2.5 and O3, and provide a promising therapeutic strategy for treating respiratory diseases caused by unavoidable exposure to these pollutants.