Specific interaction of pancreatic elastase and leucocytes to produce oxygen radicals and its implication in pancreatitis.

Abstract

Many previous reports using experimental animal models of pancreatitis have suggested that oxygen free radicals play an important part in initiation and development of pancreatitis. Infiltration of inflammatory cells -that is, neutrophils, lymphocytes, and monocytes -has been seen in damaged pancreatic glands of animal models and patients with pancreatitis. As neutrophils are known to be the highest producer of oxygen free radicals among these inflammatory cells, it seems plausible that oxygen free radicals produced by neutrophils have some pathoaetiological meaning in pancreatitis. This study measured the superoxide production by neutrophils obtained from patients with acute and chronic pancreatitis and then examined the effects of pancreatic enzymes on superoxide production. Patients showed significantly higher superoxide production by 4p-phorbol 123-myristate 13ot-acetate (PMA) stimulated neutrophils than healthy controls. Among the three pancreatic enzymes, amylase, trypsin, and elastase, elastase was the only one that increased the superoxide production by PMA stimulated neutrophils, by an increment of 15-fold. It also increased the activity of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase prepared from PMA stimulated neutrophils by a factor of 2-1. High affinity and low affinity binding sites for elastase on neutrophils were identified. These results suggest that elastase plays a part in the development of pancreatitis by enhancing superoxide production of neutrophils.

Menadione-induced Reactive Oxygen Species Generation via Redox Cycling Promotes Apoptosis of Murine Pancreatic Acinar Cells

“…Recent studies have demonstrated NAD(P)H oxidase activity (34) and inhibition of superoxide production by DPI in a pancreatic cancer cell line (35). Current evidence suggests that ROS production is enhanced in neutrophils obtained from patients with acute pancreatitis (36), and ROS derived from neutrophil NADPH oxidase may play an important role in implementing damage in experimental acute pancreatitis (37). The lack of effect of DPI observed in the present study would strongly suggest that acinar cell NAD(P)H oxidase is not responsible for the generation of ROS by menadione.…”

Oxidative Stress Induced Cytokine Production in Isolated Rat Pancreatic Acinar Cells: Effects of Small-Molecule Antioxidants

“…Actually, the superoxide production by neutrophils treated with PMA in pancreatitis patients was significantly higher than in healthy controls [5]. Among ROS, superoxide is the first reduction product of molecular oxygen.…”

“…Neutrophils are known to be the most intense producers of reactive oxygen species (ROS) among inflammatory cells. Actually, the ROS production of neutrophils obtained from patients with acute pancreatitis was enhanced [5]. The antioxidant status (plasma levels of glutathione and ascorbic acid) was decreased in patients with chronic pancreatitis [6].…”

The anti-inflammatory and antioxidant effects of thymoquinone on ceruleine induced acute pancreatitis in rats

“…In a limited number of previous studies, long-term oral administration of TQ may be effective in diseases where infl ammation and reactive oxygen species (ROS) are a prominent factor, but the pathophysiology of this effect is unclear (17,18). Although several studies show that it is not clearly elucidated in the pathogenesis of acute pancreatitis, infl ammation and ROS have an important role in the pathogenesis (19,20). The literature search shows that there is no study related to TQ effect on infl ammation, oxidative status and cytoprotective effect in acute pancreatitis model.…”