田中 健一郎

Health hazards caused by air pollutants are increasing worldwide (SDGs 3.9), but no established prevention methods exist. Recently, we showed that intraperitoneal administration of epigallocatechin gallate (EGCG) prevents air pollutant-induced acute lung injury. To establish EGCG ingestion as a preventive method, the efficacy of oral EGCG administration needs to be analyzed, as it is easier than that of intraperitoneal administration. Therefore, we analyzed the effects of oral EGCG administration and ad libitum consumption of an EGCG-containing diet in mice. The combination of 0.2% EGCG-containing diet and oral EGCG administration (200 mg/kg) significantly inhibited the urban aerosol (UA)-induced acute lung injury, although each treatment alone was ineffective. Specifically, compared with the UA group, the combination group showed 37.3% decrease in total cell count, 30.5% decrease in neutrophil count, 52.6% decrease in protein level, and 39.6% decrease in dsDNA level in the bronchoalveolar lavage fluid. This combination also significantly inhibited air pollutant-induced increases in proinflammatory cytokine and chemokine expression (e.g., tumor necrosis factor-α) and ROS production in mouse lungs. Moreover, this combination increased the expression of antioxidant factors, such as nuclear factor E2-related factor 2, in whole blood. Thus, this EGCG-based intervention combination limits UA-induced acute lung injury by increasing antioxidant expression. SUMMARY: The effects of a combination of EGCG-based interventions were analyzed. The combination prevented air pollutant-induced lung inflammatory responses. The combination suppressed air pollutant-induced ROS production in the lungs. The combination increased the expression of various antioxidants in whole blood.

<jats:p>Although Sustainable Development Goal 3.9 states the global goal of reducing air pollution-related death and disease, innovative ways to reduce air pollution-related deaths and diseases have not yet been established. To address this issue, we have established animal models using urban air dust containing the major air pollutants, suspended particulate matter (PM<jats:sub>10</jats:sub>) and fine particulate matter (PM<jats:sub>2.5</jats:sub>), and are promoting research to discover protective factors in the respiratory tract where air pollutants first reach the human body. Therefore, in this Perspective manuscript, we provide an overview of our research on the preventive effects of the endogenous protein metallothionein on air pollutant-dependent lung injury and prospects for the clinical application of metallothionein inducers. We hope that this manuscript will help to solve health hazards caused by air pollution.</jats:p>

Health problems caused by air pollutants, such as fine particulate matter, are becoming more prevalent worldwide, and there is an urgent need to develop prevention and treatment strategies to combat this increase. A main mechanism by which air pollutants cause health problems is by entering the respiratory system and increasing oxidative stress. Oleanolic acid (OA) is a natural pentacyclic triterpenoid compound found in various plants that exhibits many physiological effects, including antioxidant, anticancer, and anti-inflammatory effects. However, the effect of OA on lung injury caused by air pollutants has not been reported. We therefore analyzed the effect of OA using a mouse model of particulate matter (PM)-induced lung injury. Oral administration of OA (5-80 mg/kg) to male ICR mice suppressed PM-induced increases in inflammatory cell counts, protein levels, and dsDNA levels in bronchoalveolar lavage fluid; however, the effects were not significant. We therefore analyzed the efficacy of intravenous administration using OA encapsulated in polyethylene glycol-modified liposomes (OA-Lipo). Intravenous administration of OA-Lipo (20-100 μg/kg) was more effective against PM-induced lung injury at lower doses than oral administration. OA-Lipo also significantly suppressed increased expression of inflammatory cytokines and chemokines and ROS production in PM-exposed mice. Furthermore, intravenous administration of OA-Lipo increased the expression of various antioxidant factors in the lungs of mice. Based on these results, we believe that OA-Lipo exerts an antioxidant effect by increasing the expression of various antioxidant factors, thereby preventing the development of lung injury caused by air pollutants.