3-methyladenine ameliorates acute lung injury by inhibiting oxidative damage and apoptosis
Xiong Lei,
Xiling Liu,
Jia Yu,
Kai Li,
Lijing Xia,
Shanshan Su,
Pengcheng Lin,
Dan Zhang,
Yuping Li
Affiliations
Xiong Lei
The Key Laboratory of Interventional Pulmonology of Zhejiang Province, Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
Xiling Liu
The Key Laboratory of Interventional Pulmonology of Zhejiang Province, Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
Jia Yu
The Key Laboratory of Interventional Pulmonology of Zhejiang Province, Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
Kai Li
The First School of Medicine, School of Information and Engineering, Wenzhou Medical University, Wenzhou, China
Lijing Xia
The Key Laboratory of Interventional Pulmonology of Zhejiang Province, Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
Shanshan Su
The Key Laboratory of Interventional Pulmonology of Zhejiang Province, Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
Pengcheng Lin
The Key Laboratory of Interventional Pulmonology of Zhejiang Province, Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
Dan Zhang
The Key Laboratory of Interventional Pulmonology of Zhejiang Province, Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China; Corresponding author. The Key Laboratory of Interventional Pulmonology of Zhejiang Province, Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Wenzhou Medical University, South Baixiang, Ouhai District, Wenzhou, Zhejiang Province, 325015, China.
Yuping Li
The Key Laboratory of Interventional Pulmonology of Zhejiang Province, Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China; Corresponding author. The Key Laboratory of Interventional Pulmonology of Zhejiang Province, Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Wenzhou Medical University, South Baixiang, Ouhai District, Wenzhou, Zhejiang Province, 325015, China.
Background: Acute lung injury (ALI) is a condition characterized by inflammation and oxidative damage. 3-methyladenine (3-MA) has great potential for regulating apoptosis, but its regulatory role in ALI is unknown. Methods: Lipopolysaccharide (LPS)-treated mice and tert-butyl hydroperoxide (TBHP)-treated bronchial epithelial cells were used to simulate in vivo and in vitro ALI models, respectively. In vivo, lung injury was assessed by histopathological analysis and lung injury scoring. The total cell count, protein content, and inflammatory factors in bronchoalveolar lavage fluid (BALF) were examined. The level of apoptosis in lung tissue was assessed through TUNEL staining. In the vitro ALI model, cell viability and levels of reactive oxygen species and apoptosis were assessed. Results: 3-MA pretreatment ameliorated lung injury, including intra-alveolar hemorrhage and inflammatory cell accumulation, both in vitro and in vivo. 3-MA pretreatment also decreased inflammatory factor levels in the BALF. 3-MA pretreatment alleviated oxidative damage, decreased reactive oxygen species levels, and attenuated morphological changes. TUNEL and Annexin V-FITC/PI staining revealed that pretreatment with 3-MA reduced the level of apoptosis. 3-MA pretreatment significantly decreased the expression of caspase-3 and Bax but increased the expression of Bcl-2 in ALI. Mechanistically, 3-MA pretreatment also affected the PKCα/NOX4 and Nrf2 pathways, which decreased the level of apoptosis in ALI. Conclusions: 3-MA pretreatment inhibited inflammation and oxidative damage in ALI and inhibited apoptosis to mitigate ALI in part by inhibiting the PKCα/NOX4 pathway and activating the Nrf2 pathway. Based on these results, 3-MA might be a viable medication to treat with ALI.
