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Reappraisal of xenobiotic-induced, oxidative stress-mediated cellular injury in chronic pancreatitis: a systematic review Siriwardena AKWorld J Gastroenterol 2014[Mar]; 20 (11): 3033-43AIM: 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. 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.|*Oxidative Stress[MESH]|Acinar Cells/enzymology[MESH]|Animals[MESH]|Antioxidants/therapeutic use[MESH]|Cytochrome P-450 Enzyme System/*metabolism[MESH]|Enzyme Induction[MESH]|Glutathione Transferase/metabolism[MESH]|Hepatocytes/enzymology[MESH]|Humans[MESH]|Inhalation Exposure[MESH]|Micronutrients/*deficiency[MESH]|Pancreatitis, Chronic/*chemically induced/drug therapy/enzymology[MESH]|Superoxide Dismutase/metabolism[MESH]|Xenobiotics/*adverse effects[MESH] |
