Lactoferrin Alleviates LPS-Induced Oxidative Stress and Necroptosis in Liver by Promoting Mitophagy

Lactoferrin (LF) is an important component of dairy products. Studies have shown that LF has a protective effect against liver injury, but the mechanism of action remains incompletely understood. Lipopolysaccharide (LPS), a key component of bacterial endotoxins, can lead to liver injury when exposure is excessive. Necroptosis is a newly identified type of programmed cell death characterized by cell swelling, rupture, and necrosis, and its excessive activation contributes to tissue damage. In this study, we demonstrated that LF alleviates LPS-induced oxidative stress and necroptosis in liver cells by modulating the ROS-RIPK1-RIPK3 pathway. In further mechanistic studies, we discovered that LF promotes mitophagy in liver cells to promptly remove damaged mitochondria caused by LPS, thereby reducing the increase in reactive oxygen species (ROS) levels associated with damaged mitochondria and alleviating oxidative stress and necrosis. To validate our findings, we used mitophagy inhibitor cyclosporin A (CsA) as a negative control, and the results confirmed our findings. These results provide novel strategies and insights into utilizing LF to alleviate LPS-induced liver injury.