Lidocaine attenuates hypoxia/reoxygenation-induced inflammation, apoptosis and ferroptosis in lung epithelial cells by regulating the p38 MAPK pathway

Lung ischemia-reperfusion (I/R) injury poses a serious threat to human health, worldwide. The current study aimed to determine the role of lidocaine in A549 cells, in addition to the involvement of the p38 MAPK pathway. Oxygen deprivation/reoxygenation-induced A549 cells were utilized to simulate I/R injury in vitro. Cell viability and apoptosis were detected using MTT and TUNEL assays, respectively. The levels of IL-6, IL-8, TNF-α, malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase, iron and reactive oxygen species (ROS) were measured using corresponding commercial kits. The corresponding protein expression levels were also measured using western blotting. Moreover, a monolayer cell paracellular permeability assay was performed to determine the permeability of A549 cells. The results demonstrated that, whilst lidocaine had no influence on untreated A549 cells, it significantly increased the viability of hypoxia/reoxygenation (H/R)-induced A549 cells. A549 cell apoptosis and the release of inflammatory cytokines in the H/R group were decreased after the addition of lidocaine. When compared with the H/R group, increased MDA level and decreased SOD level were observed in H/R-induced A549 cells following lidocaine treatment. In addition, the permeability of H/R-induced A549 cells was markedly decreased following lidocaine treatment. Compared with the H/R group, the expression levels of tight junction and ferroptosis-related proteins were significantly upregulated by lidocaine, whereas the expression of transferrin was downregulated. However, p79350, an agonist of p38, reversed the effects of lidocaine on H/R-induced A549 cells. In conclusion, lidocaine exerted a protective role in HR-induced lung epithelial cell injury, which may serve as a potential agent for the treatment of patients with lung I/R injury.