[Role of free radicals in the development of severe acute pancreatitis].

Acute pancreatitis is an inflammatory disease which leads to acinar cell damage, interstitial edema, and hemorrhage. Some patients develop severe acute pancreatitis and result in multiple organ dysfunction syndrome. Acute pancreatitis is initiated by the activation of pancreatic enzyme in acinar cells. Following activation of trypsinogen into trypsin, local inflammation is initiated and activated inflammatory mediators are produced. Polymorphonuclear neutrophils, macrophages, and lymphocytes release lysosomal enzymes, oxygen free radicals, vasoactive substances, and proinflammatory mediators. In the course of the development of acute pancreatitis oxygen-free radicals and their derivatives play an important role as the molecular trigger in constituting lesions in the pancreas. Damaged acinar cells as well as activated neutrophils and macrophages produce large amount of oxygen radicals in acute pancreatitis. The hydrogen peroxide, superoxide, the hydroxyl radical, and singlet oxygen are key elements capable of cellular injury in acute pancreatitis. These highly reactive species cause various reactions, such as destruction of lipid membranes by peroxidation of fatty acids and destruction of lysosomal membranes. The oxygen radicals generated in the circulation might injure the capillary endothelium, and play an important role in accelerating the progression of acute pancreatitis. The imbalance of oxygen radical generating and oxygen radical scavenging processes is considered to lead to the cell injury in acute pancreatitis. These oxygen radicals are not only restricted in the pancreatic tissue, but involved in the systemic manifestation of the disease, particularly in the lungs, liver, and blood.