Pentoxifylline ameliorates cerulein-induced pancreatitis in rats: Role of glutathione and nitric oxide

Reactive oxygen radicals, nitric oxide, and cytokines have been implicated in the initiation of pancreatic tissue damage and impairment of the pancrea tic microcirculation in acute pancreatitis. Pentoxifylline is a methylxanth ine derivative with rheologic and marked anti-inflammatory properties and i nhibits the production of proinflammatory cytokines. We have examined wheth er pentoxifylline ameliorates interstitial edema, inflammatory infiltrate, and glutathione depletion associated with cerulein-induced pancreatitis. Co treatment of animals with pentoxifylline significantly reduced cerulein-ind uced pancreatic inflammation and edema and attenuated the depletion of panc reatic glutathione and the increase in serum lipase activity, nitrate, and tumor necrosis factor-alpha levels. Pentoxifylline also prevented both mito chondrial swelling and damage to mitochondrial cristae caused by cerulein. Our findings provide an experimental basis for using pentoxifylline to atte nuate inflammatory responses within the pancreas in acute pancreatitis and as an adjuvant in the treatment of acute pancreatitis.