Potential role of NADPH oxidase in pathogenesis of pancreatitis

Abstract

Studies have demonstrated that reactive oxygen species (ROS) are closely related to inflammatory disorders. Nicotinamide adenine dinucleotide phosphate oxidase (NOX), originally found in phagocytes, is the main source of ROS in nonphagocytic cells. Besides directly producing the detrimental highly reactive ROS to act on biomolecules (lipids, proteins, and nucleic acids), NOX can also activate multiple signal transduction pathways, which regulate cell growth, proliferation, differentiation and apoptosis by producing ROS. Recently, research on pancreatic NOX is no longer limited to inflammatory cells, but extends to the aspect of pancreatic acinar cells and pancreatic stellate cells, which are considered to be potentially associated with pancreatitis. In this review, we summarize the literature on NOX protein structure, activation, function and its role in the pathogenesis of pancreatitis.

Inhibition of pancreatic oxidative damage by stilbene derivative dihydro-resveratrol: implication for treatment of acute pancreatitis

“…For the evolution of oxidative stress, the membrane-bound NADPH oxidase system is generally considered as the major potential source of free radicals. Previous studies of ours and others showed that the activity of NADPH oxidase positively correlated to the severity of pancreatic oxidative damage in acute pancreatitis 26 34 . Moreover, it has been suggested that NF-κB activation was induced by NADPH oxidase-mediated formation of ROS 35 .…”

“…In this regard, the mechanism underlying the protective action of dihydro-resveratrol in pancreatic oxidative damage was of our particular interest. Not limited to the pancreas, the major potential source of ROS in various inflammatory conditions appeared to be the membrane-bound NADPH oxidase and xanthine oxidase systems 26 . For the activation of these ROS-generating systems, the oxidant-sensitive transcription factor NF-κB is suggested to be the principal switch, particularly during the acute stage of inflammation 27 28 .…”

Severity of pancreatitis-associated intestinal mucosal barrier injury is reduced following treatment with the NADPH oxidase inhibitor apocynin

“…In addition, the involvement of NOX has been studied in several models of acute pancreatitis and has been recognized to contribute to its progression ( 7 , 16 – 18 ). Pancreatitis-induced release of inflammatory factors, cytokines and growth factors may be responsible for local and distant organ NOX activation ( 19 ), thus resulting in further development of acute pancreatitis. It has previously been reported that apocynin treatment reduces serum levels of TNF-α, IL-1β and NF-κB, and intercellular adhesion molecule 1 expression, and decreases the severity of acute lung inflammation ( 20 ).…”

“…It has previously been demonstrated that apocynin significantly inhibits the expression levels of TNF-α and IL-1β, which are potent triggers associated with leukocyte migration, and that suppression of NOX activity by apocynin results in attenuation of ROS-mediated signal transduction and inducible nitric oxide synthase expression in lipopolysaccharide + interferon γ-stimulated microvascular endothelial cells ( 20 ). In addition, evidence suggests that inflammatory cell infiltration, including infiltration of TNF-α, IL-1β and IL-6, is an early and vital event in acute pancreatitis, which leads to local and systemic complications ( 19 ). Data from the present study demonstrated that these cytokines were increased following induction of SAP; however, their serum levels were reduced in rats treated with apocynin.…”

“…ROS are able to induce cytokine expression, apoptosis, and NF-κB, MAPK and Janus kinase/signal transducer and activator of transcription pathway activation, thus regulating inflammation and apoptosis in pancreatic acinar cells ( 19 ). Consequently, NOX, NF-κB and MAPK may be involved in the pathogenesis of acute pancreatitis ( 33 ).…”