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 selflimiting, 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.

PRMT7-Dependent Transcriptional Activation of Hmgb2 Aggravates Severe Acute Pancreatitis by Promoting Acsl1-Induced Ferroptosis

“…It has been suggested that ferroptosis exacerbates pancreatic injury in AP. 50 Recent research indicates that elevated levels of extracellular trypsin increase susceptibility to ferroptosis rather than apoptosis and necroptosis in pancreatic acinar cells. 51 The protective effects against AP can be observed by the treatment of β-hydroxybutyrate, 52 Wedelolactone, 12 and Ginsenoside Rg3 53 through the inhibition of ferroptosis of pancreatic acinar cells.…”

Ferroptosis in Acute Leukemia

“…[100] Recent Advances of Ferroptosis in AL In recent years, studies related to ferroptosis have emerged, and many studies have shown that ferroptosis is closely related to the occurrence and development of tumors. [26,38,[101][102][103][104] Here, we focus on AL and report that ferroptosis affects the occurrence and development of AL through various pathways, including various signaling pathways, natural extracts, drugs, compounds, ferroptosisrelated molecules, and so on [Figure 3 and Table 1].…”

Ca/Fe-Based Nanozymes Relieve Severe Acute Pancreatitis by Ferroptosis Regulation and Reactive Oxygen Species Scavenging

“…15 As a form of regulation of programmed cell death, ferroptosis is involved in the damage process of acinar cells in SAP, which can disrupt the balance between ROS production induced by iron accumulation and the antioxidant system within lipid peroxidation. 16,17 As a lipid repair enzyme, GPX4 is a key factor of ferroptosis, and the dysfunction or abnormal level of FTH1 will cause an increase in intracellular iron amount, allowing us to promote the occurrence of ferroptosis. 16,18 However, research of SAP treatment is still at a preliminary stage of exploration, and the development of novel nanozymebased drugs for inhibition of ferroptosis to protect organs in SAP remains to be challenging.…”

“…16,17 As a lipid repair enzyme, GPX4 is a key factor of ferroptosis, and the dysfunction or abnormal level of FTH1 will cause an increase in intracellular iron amount, allowing us to promote the occurrence of ferroptosis. 16,18 However, research of SAP treatment is still at a preliminary stage of exploration, and the development of novel nanozymebased drugs for inhibition of ferroptosis to protect organs in SAP remains to be challenging.…”

“…Oxidative stress (OS) plays a major role in SAP, causing several macrophages to penetrate the inflammatory area. , Both NADPH oxidase and mitochondrial dysfunction are the major causes of OS in SAP, and hydrogen peroxide (H 2 O 2 ), as the second messenger of NADPH oxidase, is the major source of reactive oxygen species (ROS) in inflammation. , Subsequently, OS can further spread the local and systemic inflammation resulting from the activation of neutrophils’ inflammatory response to acinar cell injury . As a form of regulation of programmed cell death, ferroptosis is involved in the damage process of acinar cells in SAP, which can disrupt the balance between ROS production induced by iron accumulation and the antioxidant system within lipid peroxidation. , As a lipid repair enzyme, GPX4 is a key factor of ferroptosis, and the dysfunction or abnormal level of FTH1 will cause an increase in intracellular iron amount, allowing us to promote the occurrence of ferroptosis. , However, research of SAP treatment is still at a preliminary stage of exploration, and the development of novel nanozyme-based drugs for inhibition of ferroptosis to protect organs in SAP remains to be challenging.…”