Oxidative stress in chronic pancreatitis: pathophysiological relevance and management

Chronic pancreatitis (CP) is a progressive, inflammatory disease of the pancreas leading to slow destruction of pancreatic parenchyma and progressive fibrosis. The pathophysiological mechanism of CP is not well understood. A pathophysiologic role of oxidative stress in CP has, however, been suggested in recent years. Pancreatic acinar cells contain phase I cytochrome P450 (CYP 450) biotransforming enzymes and phase II conjugation reactions for the metabolism of xenobiotics. The oxidative stress in the acinar cell may result from generation of free radicals through CYP induction, concurrent exposure to a chemical that undergoes bioactivation, and insufficiency of micronutrients that are required to sustain antioxidant (AO) capacity. Studies have shown that there is indeed a state of oxidative stress as evidenced by increased levels of products of oxidative stress and reduced AO capacity in patients with CP. A recent randomized, controlled trial has shown beneficial effect of AO therapy in CP; a combination of AOs (0.54 g ascorbic acid, 9000 IU β-carotene, 270 IU α-tocopherol, 600 μg organic selenium, and 2 g methionine per day in divided doses) led to significant reductions in pain and oxidative stress in patients with CP. Similar studies from other centers and multicenter studies should confirm that oxidative stress plays an important role in the pathophysiology of CP and supplementation with AOs leads to significant pain relief in patients with this disease.