title: Reappraisal of xenobiotic-induced, oxidative stress-mediated cellular injury in chronic pancreatitis: a systematic review.
abstract: OBJECTIVE
  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 1(st) January 1990 to 31(st) 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Ajith K Siriwardena, Hepatobiliary Surgery Unit, Manchester Royal Infirmary, Manchester M13 9WL, United Kingdom.
authors.forename: Ajith K
authors.initials: AK
authors.lastname: Siriwardena
mesh_terms: D061354:Acinar Cells / Q000201:enzymology; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004790:Enzyme Induction; D005982:Glutathione Transferase / Q000378:metabolism; D022781:Hepatocytes / Q000201:enzymology; D006801:Humans; D019570:Inhalation Exposure; D018977:Micronutrients / Q000172:deficiency*; D018384:Oxidative Stress; D050500:Pancreatitis, Chronic / Q000139:chemically induced* / Q000188:drug therapy / Q000201:enzymology; D013482:Superoxide Dismutase / Q000378:metabolism; D015262:Xenobiotics / Q000009:adverse effects*
chemical_list: D000975:Antioxidants; D018977:Micronutrients; D015262:Xenobiotics; D003577:Cytochrome P-450 Enzyme System; D013482:Superoxide Dismutase; D005982:Glutathione Transferase
keywords: Cellular injury; Chronic pancreatitis; Cytochrome P450; Oxidative stress; Xenobiotics