The Role of Iron and Ferroptosis in the Pathogenesis of L-Arginine-Induced Acute Pancreatitis.

Abstract

Acute pancreatitis (AP) is an inflammatory disease characterized by destruction of acinar cells. Although ferroptosis, an iron-dependent form of the programmed cell death, participates in the development of various inflammatory diseases, its implication in L-arginine-induced AP model was not clarified. This study aims to verify the involvement of ferroptosis in L-arginine-induced AP mice. The mouse model of AP was induced by intraperitoneal injection of L-arginine and then confirmed by inspection of the pancreatic tissues and analysis of blood serum. The pancreas samples were examined by light and transmission electron microscopy followed by ELISA, immunofluorescence, Western blotting, and qPCR. In AP mice, activities of serum amylase and lipase, as well as the levels of proinflammatory cytokines, increased in parallel with accumulation of iron and LPO products. There were inflammatory injuries and necrosis in the pancreatic tissues. Electron microscopy of pancreatic tissue samples revealed shrunk mitochondria with increased membrane density. In addition, expression of transferrin receptor 1 in AP mice significantly increased (p < 0.01), while expression of glutathione peroxidase 4 significantly decreased (p < 0.01). The study revealed signs of ferroptosis in mice with AP induced by L-arginine.