Melatonin ameliorates acute necrotizing pancreatitis by the regulation of cytosolic Ca2+ homeostasis.
OBJECTIVE
This study aims to investigate the relationship between the protective effects of melatonin in pancreas and the expression of sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA) and Na(+)/Ca(2+) exchanger (NCX) in rats with acute necrotizing pancreatitis (ANP), to verify whether melatonin ameliorates ANP by alleviating calcium overload.


METHODS
Ninety-six male Sprague-Dawley rats were randomly divided into four groups (sham operation group, ANP group, melatonin treatment group, melatonin contrast group). ANP was induced by the retrograde injection of 4% taurocholate (1 ml/kg body weight) into the biliopancreatic duct. Melatonin (50 mg/kg body weight) was administered 30 min before the induction of ANP in the melatonin treatment group. Rats in each group were euthanized at 1, 4, and 8 h after ANP induction. Pancreatic tissues were removed to measure SERCA and NCX levels and cytosolic calcium ion (Ca(2+)) concentration ([Ca(2+)](i)).


RESULTS
At each time point, SERCA and NCX levels in the melatonin treatment group were significantly higher than that in the ANP group, and lower than that in the sham group and the melatonin contrast group. These levels did not differ between the 4- and 8-h time points in the ANP group. [Ca(2+)](i) in pancreatic acinar cells was higher in the melatonin treatment group than in the sham group and the melatonin contrast group, but lower than in the ANP group, at each time point.


CONCLUSIONS
Melatonin can reduce pancreatic damage via the up-regulation of SERCA and NCX expression, which can alleviate calcium overload in pancreatic acinar cells.
Department of Gastroenterology and Hepatology, First Affiliated Hospital of Wenzhou Medical College, Wenzhou, 325000 Zhejiang, China.
Jiaping
J
Huai
Yingying
Y
Shao
Xuecheng
X
Sun
Yin
Y
Jin
Jiansheng
J
Wu
Zhiming
Z
Huang
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D015536:Down-Regulation; D008297:Male; D008550:Melatonin / Q000627:therapeutic use*; D019283:Pancreatitis, Acute Necrotizing / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000096:biosynthesis / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000096:biosynthesis / Q000378:metabolism; D015854:Up-Regulation
D019831:Sodium-Calcium Exchanger; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D008550:Melatonin; D002118:Calcium