title: The circadian rhythm of melatonin modulates the severity of caerulein-induced pancreatitis in the rat.
abstract: Melatonin, an antioxidant, protects the pancreas against acute inflammation but, although this indole is released mainly at night, no study has been undertaken to determine circadian changes of plasma melatonin levels and the severity of acute pancreatitis. The aims of this study were: (a) to compare the severity of caerulein-induced pancreatitis (CIP) produced in the rat during the day and at the night, and (b) to assess the changes of plasma melatonin level and the activity of an antioxidative enzyme; superoxide dismutase (SOD), in the pancreas subjected to CIP during the day time and at night without or with administration of exogenous melatonin or its precursor; l-tryptophan. Rats were kept in 12 hr light/dark cycle. CIP was induced by subcutaneous infusion of caerulein (5 microg/kg/hr for 5 hr). Melatonin (5 or 25 mg/kg) or l-tryptophan (50 or 250 mg/kg) was given intraperitoneally 30 min prior to the start of CIP. CIP induced during the day time was confirmed by histological examination and manifested by pancreatic edema, and rises of amylase and lipase plasma activities (by 400 and 500%, respectively), whereas pancreatic SOD, pancreatic blood flow (PBF) and oxygen consumption by pancreatic tissue (VO(2)) were decreased by 70, 40 and 45%, respectively, as compared with the appropriate controls. All morphological and biochemical parameters of CIP induced at night were significantly less severe, compared with those recorded during the light phase. Plasma melatonin immunoreactivity was significantly higher during the night, than during the day, especially following administration of melatonin or its precursor, which reversed all manifestations of CIP. In conclusion, a circadian rhythm modulates the severity of CIP with a decrease of pancreatitis severity during the night compared with that at the day time and this may be due to the increased plasma level of melatonin and higher activity of SOD in the pancreas.
authors.affiliation: Department of Medical Physiology, Faculty of Health Care, Medical Faculty, Jagiellonian University CM, 31-531 Krakow, Poland. mpjawore@cyf-kr.edu.pl
authors.forename: Jolanta
authors.initials: J
authors.lastname: Jaworek
authors.forename: Stanisław J
authors.initials: SJ
authors.lastname: Konturek
authors.forename: Romana
authors.initials: R
authors.lastname: Tomaszewska
authors.forename: Anna
authors.initials: A
authors.lastname: Leja-Szpak
authors.forename: Joanna
authors.initials: J
authors.lastname: Bonior
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Nawrot
authors.forename: Magdalena
authors.initials: M
authors.lastname: Palonek
authors.forename: Jerzy
authors.initials: J
authors.lastname: Stachura
authors.forename: Wiesław W
authors.initials: WW
authors.lastname: Pawlik
mesh_terms: D000681:Amylases / Q000378:metabolism; D000818:Animals; D002108:Ceruletide / Q000633:toxicity; D002940:Circadian Rhythm; D003624:Darkness; D004305:Dose-Response Relationship, Drug; D008049:Lipase / Q000378:metabolism; D008297:Male; D008550:Melatonin / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D009929:Organ Size / Q000187:drug effects; D010100:Oxygen / Q000378:metabolism; D010179:Pancreas / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010195:Pancreatitis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology* / Q000517:prevention & control; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects; D013482:Superoxide Dismutase / Q000378:metabolism; D014364:Tryptophan / Q000378:metabolism / Q000494:pharmacology
chemical_list: D002108:Ceruletide; D014364:Tryptophan; D013482:Superoxide Dismutase; D008049:Lipase; D000681:Amylases; D008550:Melatonin; D010100:Oxygen