Multiple organ injury in male C57BL/6J mice exposed to ambient particulate matter in a real-ambient PM exposure system in Shijiazhuang, China

Abstract

The development of a rodent ambient particulate matter (PM) inhalation system is critical for drawing causal inferences between PM exposure and the onset of human diseases. In this study, we constructed a real-ambient PM exposure system to investigate multi-organ injury and the reversibility of the impairments in C57BL/6 J male mice exposed to PM with a duration of up to three months in Shijiazhuang, a city with the highest PM2.5 concentration in China. This unique exposure system provided an optimal scenario for round-the-clock PM exposure absent a change in the physiochemical properties of PM and minimized the disturbance to the mice habitat. The mean concentration of PM2.5 in the exposure chambers was 89.95, 79.98, and 87.87 μg/m³ at three different time points, respectively: weeks 1-3, week 1-6, and week 1-12. The injury in multiple organs, including lung, brain, heart, testis, and intestine, was profound and was evident by the significant pathological and functional alterations. Pulmonary pathological examination revealed severe interstitial inflammatory and alveolar hemorrhage throughout the exposure, which was in line with the reduced lung function and the increased cytokine excretion in bronchoalveolar lavage fluid and blood plasma. Notably, the PM-mediated inflammatory response in different systems was correlated with the severity of the injury and the attenuation of pulmonary lesions in the recovery group. Thus, the PM2.5-induced inflammatory response, the chemical components-induced cytotoxicity, genetic damage, and oxidative stress might be implicated in the impairment of multiple murine organs. These findings revealed the severity, sensitivity, and reversibility of multi-organ injury in response to a real-ambient PM exposure.

Keywords: Inflammation; Mouse model; Multi-organ injury; Particulate matter; Real-ambient PM exposure system.