Effect of melatonin on the severity of L-arginine-induced experimental acute pancreatitis in rats.
OBJECTIVE
To determine the effect of melatonin pre- and post-treatment on the severity of L-arginine (L-Arg) -induced experimental pancreatitis in rats.


METHODS
Male Wistar rats (25) were divided into five groups. Those in group A received two injections of 3.2g/kg body weight L-Arg i.p. at an interval of 1h. In group MA, the rats were treated with 50 mg/kg body weight melatonin i.p. 30 min prior to L-Arg administration. In group AM, the rats received the same dose of melatonin 1h after L-Arg was given. In group M, a single dose of melatonin was administered as described previously. In group C the control animals received physiological saline injections i.p. All rats were exsanguinated 24 h after the second L-Arg injection.


RESULTS
L-Arg administration caused severe necrotizing pancreatitis confirmed by the significant elevations in the serum amylase level, the pancreatic weight/body weight ratio (pw/bw), the pancreatic IL-6 content and the myeloperoxidase activity, relative to the control values. Elevation of the serum amylase level was significantly reduced in rats given melatonin following L-Arg compared to rats injected with L-Arg only. The activities of the pancreatic antioxidant enzymes (Cu/Zn-superoxide dismutase (Cu/Zn-SOD) and catalase (CAT)) were significantly increased 24 h after pancreatitis induction. Melatonin given in advance of L-Arg significantly reduced the pancreatic CAT activity relative to that in the rats treated with L-Arg alone. In the liver, L-Arg significantly increased the lipid peroxidation level, and the glutathione peroxidase and Cu/Zn-SOD activities, whereas the Mn-SOD activity was reduced as compared to the control rats. Melatonin pre-treatment prevented these changes.


CONCLUSIONS
Melatonin is an antioxidant that is able to counteract some of the L-Arg-induced changes during acute pancreatitis, and may therefore be helpful in the supportive therapy of patients with acute necrotizing pancreatitis.
First Department of Medicine, University of Szeged, Faculty of Medicine, H-6720, Szeged, Koranyi fasor 8, Hungary. szabolcs@inlst.szote.u-szeged.hu
Annamaria
A
Szabolcs
Russel J
RJ
Reiter
Tamas
T
Letoha
Peter
P
Hegyi
Gabor
G
Papai
Ilona
I
Varga
Katalin
K
Jarmay
Jozsef
J
Kaszaki
Reka
R
Sari
Zoltan
Z
Rakonczay
Janos
J
Lonovics
Tamas
T
Takacs
D000208:Acute Disease; D000681:Amylases / Q000097:blood; D000818:Animals; D001120:Arginine / Q000633:toxicity*; D002374:Catalase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D008550:Melatonin / Q000627:therapeutic use*; D010195:Pancreatitis / Q000139:chemically induced / Q000188:drug therapy*; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism
D008315:Malondialdehyde; D001120:Arginine; D002374:Catalase; D013482:Superoxide Dismutase; D000681:Amylases; D008550:Melatonin