Evidence for early oxidative stress in acute pancreatitis. Clues for correction.
Pancreatic oxidative stress with depletion of pancreatic glutathione is an early feature in all tested models of acute pancreatitis, and sooner or later the problem extends to the lung, irrespective of disease severity, whether toward spontaneous recovery or death from multisystem organ failure. We, therefore, sought evidence of oxidative stress in the human disease by analyzing admission blood samples. We found it from high concentrations of oxidatively altered linoleic acid in serum and vitamin C in plasma (p < 0.001 vs controls or a group of other acute abdominal crises where the proportion of patients with admission Apache II 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), suggesting that this proximate bioactive metabolite of the essential amino acid had backtracked because its intracellular metabolism down the methionine trans-sulfuration pathway toward glutathione synthesis was disrupted. The aberrations transcended putative etiological factor, duration of symptoms, or disease severity. We conclude: (1) that oxidative stress has pervaded the vascular compartment by the time of admission in patients with acute pancreatitis, and, (2) that blood micronutrient antioxidant profiles at this stage are consistent not only with compromised intracellular capacity to synthesize/refurbish glutathione, but also vulnerability of intra- and extracellular lipid targets.
Braganza
J M
JM
Department of Medicine (Gastroenterology), Royal Infirmary, Manchester, UK.
Scott
P
P
Bilton
D
D
Schofield
D
D
Chaloner
C
C
Shiel
N
N
Hunt
L P
LP
Bottiglieri
T
T
D000111:Acetylcysteine / Q000097:blood; D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D000975:Antioxidants / Q000378:metabolism; D016002:Discriminant Analysis; D016166:Free Radical Scavengers / Q000097:blood; D006801:Humans; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000097:blood; D008875:Middle Aged; D018384:Oxidative Stress / Q000502:physiology*; D010195:Pancreatitis / Q000097:blood*; D012436:S-Adenosylmethionine / Q000097:blood
D000975:Antioxidants; D016166:Free Radical Scavengers; D008041:Linoleic Acids; D012436:S-Adenosylmethionine; D019787:Linoleic Acid; D000111:Acetylcysteine