Ferroptosis as a key player in the pathogenesis and intervention therapy in liver injury: focusing on drug-induced hepatotoxicity

Globally, drug-induced hepatotoxicity or drug-induced liver injury (DILI) is a serious clinical concern. Knowing the processes and patterns of cell death is essential for finding new therapeutic targets since there are not many alternatives to therapy for severe liver lesions. Excessive lipid peroxidation is a hallmark of ferroptosis, an iron-reliant non-apoptotic cell death linked to various liver pathologies. When iron is pathogenic, concomitant inflammation may exacerbate iron-mediated liver injury, and the hepatocyte necrosis that results is a key element in the fibrogenic response. The idea that dysregulated metabolic pathways and compromised iron homeostasis contribute to the development of liver injury by ferroptosis is being supported by new data. Various ferroptosis-linked genes and pathways have been linked to liver injury, although the molecular processes behind ferroptosis's pathogenicity are not well known. Here, we delve into the features of ferroptosis, the processes governing ferroptosis, and our current knowledge of iron metabolism. We also provide an overview of ferroptosis's involvement in the pathophysiology of liver injury, particularly DILI. Lastly, the therapeutic possibilities of ferroptosis targeting for liver injury management have been provided. Natural products, nanoparticles (NPs), mesenchymal stem cell (MSC), and their exosomes have attracted increasing attention among such therapeutics.