Abstract
Reactive oxygen radicals, nitric oxide, and cytokines have been implicated in the initiation of pancreatic tissue damage and impairment of the pancreatic microcirculation in acute pancreatitis. Pentoxifylline is a methylxanthine derivative with rheologic and marked anti-inflammatory properties and inhibits the production of proinflammatory cytokines. We have examined whether pentoxifylline ameliorates interstitial edema, inflammatory infiltrate, and glutathione depletion associated with cerulein-induced pancreatitis. Cotreatment of animals with pentoxifylline significantly reduced cerulein-induced pancreatic inflammation and edema and attenuated the depletion of pancreatic glutathione and the increase in serum lipase activity, nitrate, and tumor necrosis factor-α levels. Pentoxifylline also prevented both mitochondrial swelling and damage to mitochondrial cristae caused by cerulein. Our findings provide an experimental basis for using pentoxifylline to attenuate inflammatory responses within the pancreas in acute pancreatitis and as an adjuvant in the treatment of acute pancreatitis.
Footnotes
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Send reprint requests to: Dr. Juan Sastre, Departamento de Fisiologı́a, Universidad de Valencia, Avda. Blasco Ibañez 17, 46010 Valencia. E-mail:Juan.Sastre{at}uv.es
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↵1 This work was supported by Grants SAF97-0015 and 1FD97-1616 from the Spanish Ministry of Education and Science (J.S.) and Grant 98/1462 from the Fondo de Investigaciones Sanitarias (J.V.). This work was previously presented as oral communication in the 29th European Pancreatic Club Meeting, which was held in London, UK on July 9–12, 1997.
- Abbreviations:
- NO
- nitric oxide
- TNF-α
- tumor necrosis factor-α
- GSH
- reduced glutathione
- GSSG
- oxidized glutathione
- Received March 23, 1999.
- Accepted January 18, 2000.
- The American Society for Pharmacology and Experimental Therapeutics
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