Nicotinamide adenine dinucleotide phosphate oxidase in pancreatic diseases: Mechanisms and future perspectives

Abstract

Pancreatitis and pancreatic cancer (PC) stand as the most worrisome ailments affecting the pancreas. Researchers have dedicated efforts to unraveling the mechanisms underlying these diseases, yet their true nature continues to elude their grasp. Within this realm, oxidative stress is often believed to play a causal and contributory role in the development of pancreatitis and PC. Excessive accumulation of reactive oxygen species (ROS) can cause oxidative stress, and the key enzyme responsible for inducing ROS production in cells is nicotinamide adenine dinucleotide phosphate hydrogen oxides (NOX). NOX contribute to pancreatic fibrosis and inflammation by generating ROS that injure acinar cells, activate pancreatic stellate cells, and mediate macrophage polarization. Excessive ROS production occurs during malignant transformation and pancreatic carcinogenesis, creating an oxidative microenvironment that can cause abnormal apoptosis, epithelial to mesenchymal transition and genomic instability. Therefore, understanding the role of NOX in pancreatic diseases contributes to a more in-depth exploration of the exact pathogenesis of these diseases. In this review, we aim to summarize the potential roles of NOX and its mechanism in pancreatic disorders, aiming to provide novel insights into understanding the mechanisms underlying these diseases.

Keywords: Nicotinamide adenine dinucleotide phosphate hydrogen oxides; Pancreatitis; Pancreatic cancer; Reactive oxygen species; Mechanism

Core Tip: Nicotinamide adenine dinucleotide phosphate hydrogen oxides (NOX) plays a significant role in the development of pancreatitis and pancreatic cancer (PC) by contributing to pancreatic fibrosis and inflammation. It achieves this by generating reactive oxygen species, which damage acinar cells, activate pancreatic stellate cells, and induce macrophage polarization. Moreover, NOX promotes PC progression by interfering with abnormal cell apoptosis, initiating the epithelial to mesenchymal transition processes, and leading to cell genomic instability. A thorough understanding of NOX’s involvement in pancreatic diseases is crucial for comprehending the underlying mechanisms of pancreatitis and PC. This review provides a summary of NOX’s potential roles and mechanisms in pancreatic disorders, emphasizing areas that require further investigation.