Ajith K Siriwardena1. 1. Ajith K Siriwardena, Hepatobiliary Surgery Unit, Manchester Royal Infirmary, Manchester M13 9WL, United Kingdom.
Abstract
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 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.
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 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.
Authors: Xiaodan Wang; Marko Z Vatamaniuk; Carol A Roneker; Matthew P Pepper; Liangbiao G Hu; Rebecca A Simmons; Xin Gen Lei Journal: Antioxid Redox Signal Date: 2010-09-29 Impact factor: 8.401
Authors: G De las Heras Castaño; A García de la Paz; M D Fernández; J L Fernández Forcelledo Journal: Rev Esp Enferm Dig Date: 2000-06 Impact factor: 2.086
Authors: David C Whitcomb; Jessica LaRusch; Alyssa M Krasinskas; Lambertus Klei; Jill P Smith; Randall E Brand; John P Neoptolemos; Markus M Lerch; Matt Tector; Bimaljit S Sandhu; Nalini M Guda; Lidiya Orlichenko; Samer Alkaade; Stephen T Amann; Michelle A Anderson; John Baillie; Peter A Banks; Darwin Conwell; Gregory A Coté; Peter B Cotton; James DiSario; Lindsay A Farrer; Chris E Forsmark; Marianne Johnstone; Timothy B Gardner; Andres Gelrud; William Greenhalf; Jonathan L Haines; Douglas J Hartman; Robert A Hawes; Christopher Lawrence; Michele Lewis; Julia Mayerle; Richard Mayeux; Nadine M Melhem; Mary E Money; Thiruvengadam Muniraj; Georgios I Papachristou; Margaret A Pericak-Vance; Joseph Romagnuolo; Gerard D Schellenberg; Stuart Sherman; Peter Simon; Vijay P Singh; Adam Slivka; Donna Stolz; Robert Sutton; Frank Ulrich Weiss; C Mel Wilcox; Narcis Octavian Zarnescu; Stephen R Wisniewski; Michael R O'Connell; Michelle L Kienholz; Kathryn Roeder; M Michael Barmada; Dhiraj Yadav; Bernie Devlin Journal: Nat Genet Date: 2012-11-11 Impact factor: 38.330