Effects of octreotide on acute necrotizing pancreatitis in rabbits.
OBJECTIVE
To assess the role of oxygen-derived free radicals and cytokines in the pathogenesis of taurocholic acid-induced acute pancreatitis, and to evaluate the preventive effects of octreotide towards the development of acute pancreatitis.


METHODS
Acute pancreatitis was induced in male New Zealand white rabbits by retrograde injection of 0.8 mL/kg.b.m. of 50 g/L sodium taurocholate (NaTC) in the pancreatic duct. Sham-operated animals served as control. Octreotide 1 mg/kg.b.m. was administered subcutaneously before the induction of pancreatitis. Blood was taken from the jugular vein before and at 1, 3, 6, 12 and 24 h after pancreatitis induction. Serum activities of amylase, IL-6 and TNF-alpha and levels of malonyl dialdehyde (MDA), glutathione (GSH), glutathione peroxidase (GPx), catalase and superoxide dismutase (Mn-, Cu-, and Zn-SOD) in pancreatic tissue were measured.


RESULTS
Serum TNF-alpha and IL-6 levels increased significantly 3 h after the onset of pancreatitis, and then returned to control level. The tissue concentration of MDA was significantly elevated at 24 h, while the GSH level and GP-x, catalase, Mn-SOD, Cu-, Zn-SOD activities were all significantly decreased in animals with pancreatitis as compared to the control. Octreotide pretreatment significantly reversed the changes in cytokines and reactive oxygen metabolites. Octreotide treatment did not alter the serum amylase activity and did not have any beneficial effects on the development of histopathological changes.


CONCLUSIONS
Oxygen-derived free radicals and proinflammatory cytokines are generated at an early stage of NaTc-induced acute pancreatitis in rabbits. Prophylactic octreotide treatment can prevent release of cytokines and generation of reactive oxygen metabolites, but does not have any beneficial effects on the development of necrotizing pancreatitis.
Czakó
László
L
First Department of Medicine, University of Szeged, Szeged, PO Box 469, H-6701, Hungary. czal@in1st.szote.u-szeged.hu
Hegyi
Péter
P
Takács
Tamás
T
Góg
Csaba
C
Farkas
András
A
Mándy
Yvette
Y
Varga
Ilona Sz
IS
Tiszlavicz
László
L
Lonovics
János
J
D000818:Animals; D016207:Cytokines / Q000037:antagonists & inhibitors; D008297:Male; D015282:Octreotide / Q000494:pharmacology*; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D019283:Pancreatitis, Acute Necrotizing / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors; D013656:Taurocholic Acid
D016207:Cytokines; D017382:Reactive Oxygen Species; D013656:Taurocholic Acid; D015282:Octreotide