EVIDENCE FOR EARLY OXIDATIVE STRESS IN ACUTE-PANCREATITIS - CLUES FORCORRECTION

Pancreatic oxidative stress with depletion of pancreatic glutathione i s an early feature in all tested models of acute pancreatitis, and soo ner or later the problem extends to the lung, irrespective of disease severity, whether toward spontaneous recovery or death from multisyste m organ failure. We, therefore, sought evidence of oxidative stress in the human disease by analyzing admission blood samples. We found it f rom high concentrations of oxidatively altered linoleic acid in serum and vitamin C in plasma (p < 0.001 vs controls or a group of other acu te abdominal crises where the proportion of patients with admission Ap ache LI scores [or] 8 was similar). These changes were accompanied by subnormal levels of ascorbic acid in plasma (p < 0.001); selenium (p < 0.001), beta-carotene (p < 0.001), and alpha-tocopherol in serum (p = 0.005 for its molar ratio to cholesterol). Paradoxically, the plasma concentration of S-adenosylmethionine was elevated (p = 0.02), suggest ing that this proximate bioactive metabolite of the essential amino ac id had backtracked because its intracellular metabolism down the methi onine trans-sulfuration pathway toward glutathione synthesis was disru pted. The aberrations transcended putative etiological factor, duratio n of symptoms, or disease severity. We conclude: (1) that oxidative st ress has prevaded the vascular compartment by the time of admission in patients with acute pancreatitis, and, (2) that blood micronutrient a ntioxidant profiles at this stage are consistent not only with comprom ised intracellular capacity to synthesize/refurbish glutathione, but a lso vulnerability of intra- and extracellular lipid targets.