Melatonin reduces pancreatic prostaglandins production and protects against caerulein-induced pancreatitis in rats.
Melatonin has been used to treat experimental pancreatitis, although not all the drug's therapeutic mechanisms of melatonin have been defined. Prostaglandins (PGs) are proinflammatory mediators that exert their effects mainly locally during inflammatory diseases. The present study was undertaken to examine whether treatment with melatonin influences local PG production. An acute pancreatitis model in male Sprague-Dawley rats (225-275 g) was established by continuously infusing caerulein (15 mg/kg/hr). Mean arterial pressure and pancreatic perfusion were monitored continuously. Melatonin was delivered via the intraperitoneal route at doses of either 2 or 10 mg/kg, 30 min after caerulein injection. Malondialdehyde and glutathione levels of the pancreas and liver and the trypsinogen activation peptide levels in the serum were measured at the end of the experiment (8 hr after infusion of caerulein). Intraperitoneal injection of melatonin (2 and 10 mg/kg) reduced the reduction in systemic arterial pressure and decreased pancreatic perfusion in the rat model of caerulein pancreatitis. Moreover, melatonin treatment changed local PG production toward control level. Higher dose of melatonin was somewhat more effective in preventing the caerulein-induced alterations than was the lower dose.
Chen
Han-Ming
HM
Department of Surgery, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei, Taiwan. ming1838@yahoo.com
Chen
Jih-Chang
JC
Ng
Chip-Jin
CJ
Chiu
De-Fa
DF
Chen
Miin-Fu
MF
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002108:Ceruletide; D015232:Dinoprostone / Q000096:biosynthesis; D005978:Glutathione / Q000378:metabolism; D007975:Leukotriene B4 / Q000096:biosynthesis; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008550:Melatonin / Q000494:pharmacology / Q000627:therapeutic use*; D017551:Microdialysis; D009842:Oligopeptides / Q000378:metabolism; D010179:Pancreas / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D010195:Pancreatitis / Q000139:chemically induced / Q000517:prevention & control*; D011453:Prostaglandins / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects
D009842:Oligopeptides; D011453:Prostaglandins; C080396:trypsinogen activation peptide; D007975:Leukotriene B4; D008315:Malondialdehyde; D015121:6-Ketoprostaglandin F1 alpha; D002108:Ceruletide; D005978:Glutathione; D008550:Melatonin; D015232:Dinoprostone