Characterization of polyamine homeostasis in l-ornithine-induced acute pancreatitis in rats.
OBJECTIVE
l-Ornithine is a precursor of polyamine synthesis that is essential for cell survival. In contrast, intraperitoneal (IP) administration of a large dose of l-ornithine results in death of pancreatic acinar cells in rats. We investigated changes in pancreatic and extrapancreatic polyamine homeostasis after injection of l-ornithine and tested the effects of the stable polyamine analogue methylspermidine (MeSpd) on l-ornithine-induced pancreatitis.


METHODS
Male Wistar rats were injected IP with 3 g/kg l-ornithine and were untreated, pretreated, or treated with 50 mg/kg MeSpd IP. Rats were killed after 0 to 168 hours for determinations of polyamines and activities of ornithine decarboxylase and spermidine/spermine N(1)-acetyltransferase (SSAT). Pancreatitis severity was assessed by measuring standard laboratory and histological parameters.


RESULTS
Injection of l-ornithine paradoxically induced pancreatic spermidine catabolism, possibly via activation of SSAT, after (>6 hours) appearance of the first histological signs of acute pancreatitis. Polyamine levels generally increased in the lung and liver with the exception of lung spermidine levels, which decreased. Methylspermidine did not influence polyamine levels and SSAT activity and did not ameliorate the severity of l-ornithine-induced pancreatitis.


CONCLUSIONS
l-Ornithine-induced pancreatitis was associated with activation of pancreatic polyamine catabolism. However, administration of a metabolically stable polyamine analogue did not affect disease severity.
Biczó
György
G
First Department of Medicine, University of Szeged, Szeged, Hungary.
Hegyi
Péter
P
Sinervirta
Riitta
R
Berczi
Sándor
S
Dósa
Sándor
S
Siska
Andrea
A
Iványi
Béla
B
Venglovecz
Viktória
V
Takács
Tamás
T
Alhonen
Leena
L
Rakonczay
Zoltán
Z
D000123:Acetyltransferases / Q000378:metabolism; D000208:Acute Disease; D000818:Animals; D015317:Biogenic Polyamines / Q000378:metabolism*; D003404:Creatinine / Q000097:blood; D050884:HSP72 Heat-Shock Proteins / Q000032:analysis; D006706:Homeostasis; D020672:I-kappa B Proteins / Q000032:analysis; D053583:Interleukin-1beta / Q000096:biosynthesis; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D000072000:NF-KappaB Inhibitor alpha; D009952:Ornithine / Q000633:toxicity*; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D010195:Pancreatitis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D000099228:Diamine N-Acetyltransferase
D000123:Acetyltransferases; D015317:Biogenic Polyamines; D003404:Creatinine; D050884:HSP72 Heat-Shock Proteins; D020672:I-kappa B Proteins; D053583:Interleukin-1beta; D000072000:NF-KappaB Inhibitor alpha; D009952:Ornithine; D000099228:Diamine N-Acetyltransferase; C000606206:Nfkbia protein, rat