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Protective effect of melatonin and its precursor L ‐tryptophan on acute pancreatitis induced by caerulein overstimulation or ischemia/reperfusion
Author(s) -
Jaworek Jolanta,
LejaSzpak Anna,
Bonior Joanna,
Nawrot Katarzyna,
Tomaszewska Romana,
Stachura Jerzy,
Sendur Ryszard,
Pawlik Wiesław,
Brzozowski Tomasz,
Konturek Stanisław J.
Publication year - 2003
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1034/j.1600-079x.2003.02937.x
Subject(s) - melatonin , acute pancreatitis , medicine , endocrinology , malondialdehyde , lipid peroxidation , pancreatitis , tryptophan , pancreas , ischemia , chemistry , oxidative stress , biochemistry , amino acid
Abstract: Melatonin, a pineal secretory product, synthesized from l ‐tryptophan, has received increased attention because of its antioxidative and immunomodulatory properties. It has been detected in the gut and shown to protect the gastric mucosa, and liver from acute damage, but the role of melatonin in the protection of the pancreas against acute inflammation is not clear. The aim of this study was to investigate the effects of melatonin and its precursor, l ‐tryptophan, on caerulein‐induced pancreatitis (CIP) and on ischemia/reperfusion (I/R)‐provoked pancreatitis in rats. CIP was induced by subcutaneous infusion of caerulein to the rats (25 μ g/kg). I/R was induced by clamping of the inferior splenic artery for 30 min followed by 2 hr of reperfusion. Melatonin (10, 25 or 50 mg/hr) or l ‐tryptophan (50, 100 or 250 mg/kg) was given as a bolus intraperitoneal (i.p.) injection 30 min prior to the onset of pancreatitis. CIP and I/R were confirmed by histologic examination and manifested by typical pancreatic edema, by an increase of plasma levels of amylase (by 500% in CIP and by 40% in I/R) and the pro‐inflammatory tumor necrosis factor α (TNF α ) (by 500%). Lipid peroxidation products such as malondialdehyde (MDA) and 4‐hydroxynonenal (4‐HNE), were increased several fold in the pancreas CIP and I/R, whereas pancreatic blood flow (PBF) was significantly reduced in these animals. Pretreatment of rats subjected to CIP or to I/R with melatonin (25 or 50 mg/kg i.p.) or l ‐tryptophan (100 or 250 mg/kg i.p.) significantly reduced pancreatic edema, plasma levels of amylase and TNF α and diminished pancreatic MDA + 4‐HNE contents, while enhancing PBF, pancreatic integrity and plasma levels of the anti‐inflammatory interleukin 10 (IL‐10). This was accompanied by a marked and dose‐dependent rise of plasma melatonin immunoreactivity. Gene expression of N ‐acetyl transferase, an enzyme involved in melatonin biosynthesis, was detected in the pancreas of normal rats and was significantly enhanced in the rats with CIP. We conclude that exogenous melatonin, and that produced from l ‐tryptophan, attenuates pancreatic damage induced by CIP or by I/R and this effect may be attributable to the reduction in lipid peroxidation and TNF α release combined with an increase of plasma anti‐inflammatory IL‐10 in rats with acute pancreatitis.