Peroxidised linoleic acid and experimental pancreatitis.
High concentrations of lipid peroxidation (free-radical oxidation) products have been found in bile from patients with recurrent pancreatitis, and the principal component, after hydrolysis, has been identified as an isomerised form of linoleic acid -- typical concentration 25 mmol/l, compared with 4 mmol/l in controls. Chromatographically identical products can be generated by peroxidising linoleic acid using an ultraviolet (UV) source in the presence of albumin, whereas peroxidation by lipoxidase without albumin results in a constellation of products that bear no resemblance to those in biological fluids. These facts, and the suspicion that reflux of abnormal bile may be an initiating mechanism in acute pancreatitis, led us to investigate the effects of linoleic acid peroxidation products in the rat pancreas. Two concentrations of ultraviolet-peroxidised linoleic acid were used (3.6 mmol/l or 25 mmol/l, in a 2.09% solution of bile salts containing albumin 10 g/l) to simulate the human findings and, for comparison, the effects of lipoxidase-peroxidised linoleic acid, 25 mmol/l (in the 2.09% bile salt solution but without albumin), were also studied. 100 microliter of test solution was infused retrogradely into the pancreatic duct using a syringe pump. The results were assessed microscopically at 3-h intervals, and histologically at 12 h: if the animal died before the end of the experiment, the time of death was recorded. Both forms of peroxidised linoleic acid, 25 mmol/l, caused a greater degree of pancreatic injury than that produced by bile salts alone (e.g., macroscopic score at 3 h: ultraviolet, P less than 0.001; lipoxidase, P less than 0.05). Non-peroxidised linoleic acid 25 mmol/l caused less damage than ultraviolet-peroxidised linoleic acid 25 mmol/l, both macroscopically (3 h: P less than 0.01; 12 h: P less than 0.05) and on histology (P less than 0.01). Pancreatic haemorrhage was not a feature.
Anderson
R J
RJ
Department of Gastroenterology, Royal Infirmary, Manchester, U.K.
Jeffrey
I J
IJ
Kay
P M
PM
Braganza
J M
JM
D000208:Acute Disease; D000818:Animals; D001647:Bile Acids and Salts / Q000633:toxicity; D019787:Linoleic Acid; D008041:Linoleic Acids; D008054:Lipid Peroxides / Q000633:toxicity*; D008297:Male; D010088:Oxidoreductases; D010179:Pancreas / Q000187:drug effects / Q000473:pathology*; D010195:Pancreatitis / Q000139:chemically induced*; D051381:Rats; D011919:Rats, Inbred Strains; D014466:Ultraviolet Rays
D001647:Bile Acids and Salts; D008041:Linoleic Acids; D008054:Lipid Peroxides; D019787:Linoleic Acid; D010088:Oxidoreductases