The role of iron and ferroptosis in the pathogenesis of acute pancreatitis

ABSTRACT

Acute pancreatitis (AP) is an inflammatory disease of the pancreas. Iron is an essential element for life and is involved in many metabolic processes. Ferroptosis is a type of regulated cell death that is triggered by iron and oxidative stress. A well-established mouse AP model was adopted to study the role of iron and ferroptosis in the pathogenesis of pancreatitis. Mice were injected with cerulein to induce AP, and pancreatic tissue samples were analyzed to determine the pathology, cell death, iron deposition, expression of iron transporters, and lipid peroxidation. The role of iron was studied by giving mice extra iron or iron chelator. In vitro studies with acinar cells with ferroptosis activator and inhibitor were also performed to assess the inflammatory response. Iron was found accumulated in the pancreatic tissue of mice who suffered cerulein-induced pancreatitis. Cell death and lipid peroxidation increased in these tissues and could be further modulated by iron dextran or iron chelator. Mice given Hemin through gavage had reduced levels of GSH in pancreatic tissue and increased inflammatory response. Studies with acinar cells showed increased levels of lipid peroxidation and ferroptosis-specific mitochondrial damage when treated with ferroptosis inducer and inflammatory cytokines.

KEYWORDS:

• Ferroptosis
• acute pancreatitis
• Electron microscopy
• cell apoptosis
• inflammatory cytokines
• Lipid peroxidation
• reactive oxygen substances (ROS)

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

We indeed did not receive any external funding for our study. The expenses associated with our research, including laboratory equipment, data collection and analysis, publication fees, and other related costs, were covered by our own resources. We want to emphasize that our research was conducted independently and without external financial support, and we have adhered to rigorous methodologies to ensure the reliability and validity of our findings.