Early inhibition of prostaglandin synthesis by n-3 fatty acids determinates histologic severity of necrotizing pancreatitis.
OBJECTIVE
Previously, we observed decreased histopathological severity of acute necrotizing pancreatitis (ANP) by parenteral nutrition with n-3 fatty acids. Thus, we now sequentially analyzed the impact of n-3 fatty acids on prostaglandin and leukotriene synthesis in ANP.


METHODS
One hundred ninety-eight Sprague-Dawley rats (11 groups, n = 18) underwent intraductal glycodesoxycholat instillation and 6-hour cerulein infusion. Afterward, saline was infused in groups 2, 4, 6, 8, and 10, whereas groups 3, 5, 7, 9, and 11 received infusion rich in n-3 fatty acids (Omegaven, Fresenius Kabi, Bad Homburg, Germany). Animals were killed after 6 (group 1), 10 (groups 2 and 3), 14 (groups 4 and 5), 18 (groups 6 and 7), 22 (groups 8 and 9), and 26 hours (groups 10 and 11). The pancreas was histopathologically examined, and the pancreatic eicosanoid metabolism (prostaglandin E2, prostaglandin F1alpha [PGF1alpha], and leukotrienes) and lipid peroxidation (thiobarbituric acid-reactive substance, superoxide dismutase, and glutathione peroxidase) were analyzed.


RESULTS
Between the 14th and 26th hours, histopathologic scores (edema, inflammation, bleeding, and necrosis) were reduced in the n-3 fatty acid group compared with the corresponding saline group. Pancreatic prostaglandin E2 and PGF1alpha were decreased between the 10th and 18th hour by n-3 fatty acids; PGF1alpha was reduced after 26 hours compared with the corresponding saline group. Lipid peroxidation was decreased by n-3 fatty acids after 14 hours (thiobarbituric acid-reactive substance); however, there was no difference concerning lipid peroxidation protective enzymes (glutathione peroxidase and superoxide dismutase).


CONCLUSIONS
Parenteral therapy with n-3 fatty acids decreased histopathologic severity in ANP by early inhibition of prostaglandin (E2 and F1alpha) synthesis and reduction of lipid peroxidation.
Kilian
Maik
M
Clinic of General, Visceral, Vascular and Thoracic Surgery, Charité Campus Mitte, University Medicine in Berlin, Humboldt University of Berlin, Berlin, Germany. isletcell@aol.com
Gregor
Jan Ilga
JI
Heukamp
Ina
I
Wagner
Carsten
C
Walz
Martin Karl
MK
Schimke
Ingolf
I
Kristiansen
Glenn
G
Wenger
Frank Axel
FA
D000818:Animals; D002108:Ceruletide; D015232:Dinoprostone / Q000378:metabolism; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D005979:Glutathione Peroxidase / Q000378:metabolism; D015289:Leukotrienes / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D019283:Pancreatitis, Acute Necrotizing / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D011453:Prostaglandins / Q000096:biosynthesis*; D011460:Prostaglandins F / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D013997:Time Factors
D015525:Fatty Acids, Omega-3; D015289:Leukotrienes; D011453:Prostaglandins; D011460:Prostaglandins F; D017392:Thiobarbituric Acid Reactive Substances; D002108:Ceruletide; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D015232:Dinoprostone; C100006:prostaglandin F1