Ferroptosis and its emerging roles in acute pancreatitis

Abstract

Acute pancreatitis (AP) is a common and potentially life-threatening pancreatic inflammatory disease. Although it is usually self-limiting, up to 20% of patients will develop into severe AP. It may lead to systemic inflammatory response syndrome and multiple organ dysfunction, affecting the lungs, kidneys, liver, heart, etc. Surviving patients usually have sequelae of varying degrees, such as chronic hyperglycemia after AP (CHAP), pancreatic exocrine insufficiency, and chronic pancreatitis. Lacking specific target treatments is the main reason for high mortality and morbidity, which means that more research on the pathogenesis of AP is needed. Ferroptosis is a newly discovered regulated cell death (RCD), originally described in cancer cells, involving the accumulation of iron and the depletion of plasma membrane polyunsaturated fatty acids, and a caspase-independent RCD. It is closely related to neurological diseases, myocardial infarction, ischemia/reperfusion injury, cancer, etc. Research in the past years has also found the effects of ferroptosis in AP, pancreatic cancer, and AP complications, such as acute lung injury and acute kidney injury. This article reviews the research progress of ferroptosis and its association with the pathophysiological mechanisms of AP, trying to provide new insight into the pathogenesis and treatment of AP, facilitating the development of better-targeted drugs.