Reappraisal of xenobiotic-induced,oxidative stress-mediated cellular injury in chronic pancreatitis:A systematic review

AIM:To reappraise the hypothesis of xenobiotic induced,cytochrome P450-mediated,micronutrient-deficient oxidative injury in chronic pancreatitis.METHODS:Individual searches of the Medline and Embase databases were conducted for each component of the theory of oxidative-stress mediated cellular injury for the period from 1st January 1990 to 31st December2012 using appropriate medical subject headings.Boolean operators were used.The individual components were drawn from a recent update on theory of oxidative stress-mediated cellular injury in chronic pancreatitis.RESULTS:In relation to the association between exposure to volatile hydrocarbons and chronic pancreatitis the studies fail to adequately control for alcohol intake.Cytochrome P450(CYP)induction occurs as a diffuse hepatic and extra-hepatic response to xenobiotic exposure rather than an acinar cell-specific process.GSH depletion is not consistently confirmed.There is good evidence of superoxide dismutase depletion in acute phases of injury but less to support a chronic intraacinar depletion.Although the liver is the principal siteof CYP induction there is no evidence to suggest that oxidative by-products are carried in bile and reflux into the pancreatic duct to cause injury.CONCLUSION:Pancreatic acinar cell injury due to short-lived oxygen free radicals(generated by injury mediated by prematurely activated intra-acinar trypsin)is an important mechanism of cell damage in chronic pancreatitis.However,in contemporary paradigms of chronic pancreatitis this should be seen as one of a series of cell-injury mechanisms rather than a sole mediator.