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 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-alpha 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.
Gómez-Cambronero
L
L
Departamento de Fisiología, Facultad de Medicina, Universitat de Valencia, Valencia, Spain.
Camps
B
B
de La Asunción
J G
JG
Cerdá
M
M
Pellín
A
A
Pallardó
F V
FV
Calvete
J
J
Sweiry
J H
JH
Mann
G E
GE
Viña
J
J
Sastre
J
J
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002108:Ceruletide; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced / Q000473:pathology; D005765:Gastrointestinal Agents; D005978:Glutathione / Q000378:metabolism / Q000502:physiology*; D008049:Lipase / Q000378:metabolism; D008297:Male; D008854:Microscopy, Electron; D009569:Nitric Oxide / Q000502:physiology*; D010084:Oxidation-Reduction; D010179:Pancreas / Q000473:pathology; D010195:Pancreatitis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D010431:Pentoxifylline / Q000494:pharmacology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000975:Antioxidants; D005765:Gastrointestinal Agents; D010726:Phosphodiesterase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D002108:Ceruletide; D008049:Lipase; D005978:Glutathione; D010431:Pentoxifylline