Potential mechanisms and effects of melatonin-regulated Nrf2/HO-1 pathway on acute lung injury due to formaldehyde exposure

Abstract

Acute lung injury is a topic of great interest in critical care medicine due to its high mortality rates. The lungs are the immediate target organ for formaldehyde inhalation damage. Lung damage and fibrosis are the most important outcomes of severe and acute lung disease and pose a serious threat to human health. Melatonin (MT), a natural bioactive compound with anti-inflammatory and antioxidant properties, However, it is not clear whether MT can prevent FA-induced acute lung injury (ALI). Therefore, in this study, we aimed to evaluate the protective effects of MT and the potential mechanisms against FA-induced ALI. An environmental exposure bin was used to inhale 3 mg{middle dot}m3 FA-induced ALI, which was given intraperitoneally with different doses of MT (5/10/20 mg/kg) after successful modeling. In addition, rats were treated with Nrf2 inhibitor (ML385) to validate the signaling pathway. Lung function was measured, histopathological/morphological changes in lung tissue were assessed, and inflammatory expression and oxidation levels in lung tissue were detected. We observed that MT greatly alleviated the lung dysfunction, pathological lung injury, pulmonary edema and inflammatory response after successful modeling of FA. In additional, MT played a role in modulating the Nrf2/HO-1 signaling pathway, which effectively inhibit oxidative stress caused by FA-induced lung tissue injure. Moreover, we found that activation of the NF-{kappa}B pathway is associated with inflammation caused by this injury. Overall, our data suggest that MT inhibits the expression of oxidative stress and inflammation in lung tissue through the institutional or Nrf2/HO-1 pathway, alleviating FA-induced ALI.