Hydrogen ameliorates lung injury in a rat model of subacute exposure to concentrated ambient PM2.5 via Aryl hydrocarbon receptor

Background Ambient fine particulate matter (PM2.5) could induce lung injury. Aryl hydrocarbon receptor (AhR) is involved in the molecular mechanisms of prooxidative and pro-inflammatory effect of PM2.5. Molecular hydrogen has antioxidant properties. The protective effect and mechanism of hydrogen on PM2.5-induced lung injury remain unclear. Objectives This study aimed to determine whether hydrogen could alleviate lung injury in a rat model of subacute exposure to concentrated ambient PM2.5, and explore the mechanism related to AhR. Methods Male Wastar rats were exposed to either concentrated ambient particles (CAPs) (diameter: ≤2.5 μm, average concentration: 1328 ± 730 μg/m3) or filtered air (FA) by nose-only inhalation (5 h/day, 5 days/week for 4 weeks). Hydrogen-treated rats inhaled 66.7% hydrogen from water electrolysis for 2 h after each exposure to CAPs or FA. Results CAPs inhalation induced lung injury, as demonstrated by pulmonary function decrease, histopathological damage, mucus hypersecretion [Periodic acid-Schiff (PAS) staining for mucins, immunohistochemistry and quantitative real-time PCR (RT-qPCR) for mucin 5AC (MUC5AC) expression], increased pro-inflammatory cytokines (TNF-α, IL-8 and IL-1β) and oxidative damage indexes [malondialdehyde (MDA) and 8-isoprostane F2α (8-iso-PG)]. While, hydrogen inhalation significantly alleviated the damages mentioned above. In addition, low expression of AhR in lung tissues determined by Western Blot was found after CAPs exposure, whereas hydrogen inhibited AhR decline induced by CAPs. Conclusions High concentrations of hydrogen could ameliorate pulmonary dysfunction, airway mucus hypersecretion, oxidation damage, and inflammation response in rats exposed to concentrated ambient PM2.5. Additionally, hydrogen alleviates lung injury induced by PM2.5 possibly through AhR-dependent mechanisms.