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Intravenous Administration of Liposomes Encapsulating Oleanolic Acid Ameliorates Lung Injury Caused by Air Pollutants

Rioko Funayama,Aeri Toratani,Yui Uehara,Reno Kinoshita,M. Shimada,Rion Imai,Mikako Shimoda,Masahiro Kawahara,Susumu Hama,Ken-Ichiro Tanaka

Published 2025 in Environmental Toxicology

ABSTRACT

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.

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