Role of nonesterified fatty acids in necrotizing pancreatitis: an in vivo experimental study in rats.
BACKGROUND
In acute pancreatitis, nonesterified fatty acids (NEFA) might be released by lipase and cause tissue necrosis by their detergent properties, but this has not been established in vivo.


OBJECTIVE
To measure the release of NEFA in the blood stream, pancreatic tissue, and peritoneal cavity during taurocholate-induced acute necrotizing pancreatitis in rats.


METHODS
Ascites and blood were repeatedly sampled; after 24 hours, pancreatic lesions were scored, and NEFA were measured in the pancreas. The effects of a specific lipase inhibitor (Tetrahydrolipstatin [THL]) were also studied.


RESULTS
A slight transient increase (22%) of NEFA concentration was observed in systemic circulation but did not parallel the time course of lipase activity, arguing against an intravascular production of NEFA by circulating lipase. Pancreatic NEFA did not differ between rats with pancreatitis and control rats. NEFA in ascites increased to threefold the basal value immediately after taurocholate and decreased rapidly thereafter, whereas lipase increased later in ascites and remained elevated during the 24-hour duration of the experiment. Lipase inhibition by THL neither modified the early increase of NEFA in ascites, nor altered the macroscopic, enzymatic, and histologic evolution of pancreatitis.


CONCLUSIONS
This in vivo study does not confirm the hypothetical role of NEFA produced by pancreatic lipase in the necrotic process and its systemic complications, up to now mainly suggested on the basis of ex vivo experiments.
Paye
F
F
Instítut National de la Santé et de la Recherche Medicale Unité U410, Neuroendocrinologie et Biologie Cellulaire Digestives, Faculté Xavier Bichat, 16 rue Henri Huchard, 75018 Paris, France.
Presset
O
O
Chariot
J
J
Molas
G
G
Rozé
C
C
D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005230:Fatty Acids, Nonesterified / Q000032:analysis / Q000097:blood / Q000502:physiology*; D007700:Kinetics; D007783:Lactones / Q000494:pharmacology; D008049:Lipase / Q000037:antagonists & inhibitors; D008297:Male; D000077403:Orlistat; D010179:Pancreas / Q000378:metabolism; D019283:Pancreatitis, Acute Necrotizing / Q000139:chemically induced / Q000378:metabolism*; D010537:Peritoneum / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013656:Taurocholic Acid
D004791:Enzyme Inhibitors; D005230:Fatty Acids, Nonesterified; D007783:Lactones; D013656:Taurocholic Acid; D000077403:Orlistat; D008049:Lipase