Targeting AMPK and the Nrf2/HO-1 axis: a promising therapeutic strategy in acute lung injury

Acute lung injury (ALI) is defined as pulmonary conditions leading to severe hypoxaemia, with human acute respiratory distress syndrome (ARDS) representing its most severe manifestation [1]. The primary causes of ARDS are trauma, bacterial and viral pneumonia, sepsis and adverse drug reactions [2]. The development of effective therapeutics for ALI/ARDS remains an urgent unmet need [3]. The overall crude incidence of ALI from all sources has been estimated at 76.9 per 100 000 person-years (86.2 after age adjustment) [4]; or ∼200 000 cases per year in the USA [1]. ALI is generally associated with endothelial and epithelial cell injury, loss of alveolar–capillary membrane integrity, neutrophil influx into the lung, and release of pro-inflammatory mediators [1]. Exposure to halogen gases, such as bromine (Br2) and chlorine (Cl2), as well as to halogenated organic compounds, can cause severe ALI. Although many experimental animal models of ALI have been developed [5], halogen gas-induced ALI has been less widely studied. Halogen gas-induced ALI/ARDS remains a public health concern as it can arise from industrial occupational and accidental exposures. Despite individual case reports, there is a lack of more precise epidemiological data on the incidence of halogen-gas specific ALI [6]. Therapeutic targeting of AMPK can improve acute lung injury via upregulation of the cytoprotective enzyme heme oxygenase-1