Carbamylated erythropoietin alleviates seawater immersion-aggravated acute lung injury via inhibiting ferroptosis after Traumatic Brain Injury.

Abstract

Abstract Acute lung injury (ALI) is a life-threatening disorder associated with high morbidity and mortality rates. It is characterized by reactive oxygen species (ROS) generation and epithelial apoptosis. Ferroptosis, another form of cell death triggered by the accumulation of bioactive iron and ROS generation, has been implicated in the pathogenesis of ALI. This study aimed to explore the role of Carbamylated erythropoietin (C-EPO) in treating seawater drowning (SWD)-induced acute lung injury (SWD-ALI) and SWD-ALI aggravated by traumatic brain injury (SWD + TBI). The study established rat models of SWD-ALI and SWD + TBI-induced ALI to investigate the effects of C-EPO on ferroptosis and autophagy in these conditions. Rat models of SWD-ALI and SWD + TBI-induced ALI were created to evaluate the impact of C-EPO. Lung histopathology, tissue damage, oxidative stress, and lung injury severity were assessed to determine the effectiveness of C-EPO treatment. The study also examined the influence of C-EPO on ferroptosis and autophagy. Key proteins in the mTOR signaling pathway, including p-mTOR, P62, Beclin1, and the LC3II/LC3I ratio, were analyzed to elucidate the underlying mechanisms. C-EPO treatment significantly improved lung histopathology, reduced tissue damage, mitigated oxidative stress, and attenuated lung injury severity in the SWD-ALI and SWD + TBI-induced ALI rat models. C-EPO demonstrated protective effects against septicemia-induced ferroptosis in the lung tissue of rats with SWD + TBI-induced ALI. Furthermore, C-EPO treatment inhibited autophagy activation in SWD + TBI-induced ALI by modulating the mTOR signaling pathway, as evidenced by decreased expression of p-mTOR, P62, Beclin1, and a modified LC3II/LC3I ratio.The findings of this study suggest that C-EPO shows promise as a therapeutic agent for managing SWD-ALI and SWD + TBI-induced ALI. By targeting ferroptosis and suppressing autophagy via modulation of the mTOR signaling pathway, C-EPO provides protection against lung injury. These results contribute to a deeper understanding of the underlying mechanisms of ALI and offer valuable insights into potential therapeutic interventions for this life-threatening condition.