Title: Therapeutic effect of an oral trypsin inhibitor on pancreatic fibrosis caused by repeated administra tion of a sod inhibitor
Abstract: Introduction: Heat-stress preconditioning of mammalian pancreas has been found confer protection against pancreatitis.Heat shock is generally provided warming the animal by mechanical means, which is often impractical in using large mammals and in clinical setting.Amphetamine, a sympathomimetic drug, can elevate the body temperature as a results of enhanced endogenous lipolysis.The present study was performed to determine whether administration of amphetamine induces hyperthermia and heat shock protein (hsp) 72 expression in pancreatic cell, and to study whether this response has protective effects against secretagogue induced pancreatitis in rats.Material and Method: Male Sprague-Dawley rat were injected amphetamine(15mg/kg i.p) and body temperature was monitored every 20minute.For control studies, the rats were injected with saline.After 24hours, rats were sacrificed and the pancreas was removed from each rat and the expression of hsp72 was evaluated by Western blotting.For induction of pancreatitis, rats were injected with caerulein(20p.g/kg,intraperitoneally) at 24 hours after administration of amphetamine.The severity of pancreatitis were evaluated 5 hours after the start of caerulein injection .Results: Amphetamine treatment caused an acute rise in core body temperature to 41DC for at least 1 hour and sustained for at least 2 hours.None of rats were die during experiments.The expressions of hsp72 were consistently induced in pancreas from amphetamine treated rat compared to control rat.The severity of pancreatitis judged by pancreatic edema, hyperamylasemia, inflammatory cell infiltration and intracellular vacuolization were significantly reduced by amphetamine pretreatment.Conclusions: Amphetamine administration can induce hyperthermia and expression of hsp72 in pancreas.Preinduction of hsp72 by amphetamine has protective effect on caerulein-induced pancreatitis.These data suggested that large mammals, such as opossum and pigs, could be available for the experiments for heat shock protein. 3309