Published online Mar 21, 2014. doi: 10.3748/wjg.v20.i11.3033
Revised: November 5, 2013
Accepted: December 3, 2013
Published online: March 21, 2014
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 December 2012 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 intra-acinar depletion. Although the liver is the principal site of 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.
Core tip: This review systematically appraises the evidence for the key components of the hypothesis of environmental xenobiotic exposure leading to induction of the cytochrome P450 (CYP) system in the pancreatic acinar cell and in turn compromising the free radical quenching pathway in chronic pancreatitis. The central components of the hypothesis of xenobiotic-induced, micronutrient-deficient oxidative-stress mediated cell injury in chronic pancreatitis: xenobiotic exposure causing CYP induction, acinar CYP induction and hepatocyte mediated CYP by-products causing acinar injury by bile reflux do not withstand objective scrutiny.