Ferroptosis in Hypertriglyceridemic Acute Pancreatitis: Mechanisms and Therapeutic Implications

Ferroptosis, a iron-dependent programmed cell death characterized by iron-dependent accumulation of lipid peroxidation to lethal levels, is closely related to the pathogenesis of hypertriglyceridemic acute pancreatitis, a condition marked by lipid metabolism disorders. This paper summarizes the latest research progress in understanding the mechanistic contributions on the mechanisms of ferroptosis in HTG-AP, with a particular focus on the roles of lipid peroxidation and iron-catalyzed reactive oxygen species generation in the pathogenesis and progression of HTG-AP. It further elaborates on critical molecules-including the GPX4, ACSL4, SLC7A11 and FSP1-CoQ10-NAD(P)H and key cellular signaling pathways-including the HIF pathways, JAK-STAT pathways, PI3K/ Akt pathways closely linked to ferroptosis in HTG-AP. Understanding the pathophysiological role of hypertriglyceridemia in pancreatic injury is essential for unraveling the complex interplay between lipid and iron metabolic homeostasis. Additionally, by integrating evidence from preclinical models and human studies, this review emphasizes the importance of ferroptosis mechanisms in the treatment of HTG-AP, with the goal of identifying potential therapeutic targets and proposing innovative intervention strategies aimed at mitigating ferroptosis, potentially improving outcomes in HTG-AP.