Melatonin Attenuates Endoplasmic Reticulum Stress in Acute Pancreatitis

Objectives The objective of this study is to explore the effect of melatonin on endoplasmic reticulum stress in acute pancreatitis (AP) and the molecular mechanism. Methods Acute pancreatitis was induced in vivo in Sprague-Dawley rats by the retrograde injection of 5% taurocholate into the biliopancreatic duct and in vitro by treating AR42J cells with cerulein (10 nmol/L) plus lipopolysaccharide (LPS) (10 mg/L). The rats and cells were treated with melatonin (50 mg/kg in rats and 0.5, 1, and 2 mmol/L in AR42J cells) 30 minutes before AP was induced. After 9 hours, the cells and rat pancreas tissue were collected for Western blot, reverse transcription polymerase chain reaction, histological examination, immunohistochemistry, and immunofluorescence analysis. Results Inositol-requiring 1 (IRE1)-mediated Jun N-terminal kinase (JNK)/nuclear factor-kappa B (NF-B) pathway were activated early in AR42J cells and rat AP models. Melatonin significantly inhibited the expression of proinflammatory cytokines. Western blot and immunohistochemical results all indicated that melatonin regulated apoptosis-related protein expression. In addition, melatonin treatment resulted in significantly reduced pancreatic tissue injury, as revealed by histological changes and pathological scores. Furthermore, melatonin treatment significantly reduced the activation of IRE1-mediated JNK/NF-B pathway-related proteins. Conclusions These findings suggest that melatonin protects AR42J cells and Sprague-Dawley rats against AP-associated injury, probably through downregulation of IRE1-mediated JNK/NF-B pathways.