Melatonin protects against PM2.5-induced lung injury by inhibiting ferroptosis of lung epithelial cells in a Nrf2-dependent manner

PM2.5 refers to ambient air particulate matter with aerodynamic diameters < 2.5 mu m, which has been a global environmental problem threatening public health in recent years. Melatonin serving as one of the predominant hormones secreted by the pineal gland displays multiple pharmacological properties in various diseases. However, little is known about the possible effects of melatonin in the development of lung injury induced by PM2.5. This study was designed to explore the potential roles of melatonin as well as its possible mechanisms in PM2.5induced lung injury. In the present study, mice were intratracheally instilled with PM2.5 dissolved in sterile water to induce lung injury with or without intragastric administration of melatonin. The results showed that melatonin treatment significantly alleviated lung pathological injury and edema, apart from inhibiting inflammatory cell infiltration. Meantime, melatonin also decreased the makers of ferroptosis and lipid peroxidation products in lung tissues challenged with PM2.5. Additionally, melatonin promoted the nuclear translocation and expression of Nrf2 and the protein degradation of Keap1. However, the pulmonary protection and antiferroptosis effect of melatonin were counteracted in Nrf2-deficiency mice. In vitro experiments further demonstrated that Nrf2 knockdown could offset anti-ferroptosis effect of melatonin in MLE-12 lung epithelial cells. Taken together, our study disclosed that melatonin could relieve PM2.5-induced lung injury via inhibiting ferroptosis of lung epithelial cells by activating Nrf2. Hence, melatonin may be a promising candidate against lung injury associated with air particulate matter.

Automated summary

This study investigated the potential roles of melatonin in PM2.5-induced lung injury and found that melatonin treatment alleviated lung pathological injury, edema, and inflammatory cell infiltration. Melatonin also inhibited ferroptosis and lipid peroxidation products in lung tissues and activated Nrf2 to protect against lung injury.