A Mini-Review on the Effect of Docosahexaenoic Acid (DHA) on Cerulein-Induced and Hypertriglyceridemic Acute Pancreatitis

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  Figure 1. Proposed mechanisms of action of docosahexaenoic acid (DHA) in cerulein-induce acute pancreatitis. Cerulein induced the activation of NADPH oxidase, which produces large amounts of reactive oxygen species (ROS) in pancreatic acinar cells. ROS activate protein kinase C-δ (PKC-δ), which activates nuclear factor-κB (NF-κB). ROS also directly activate NF-κB, activator protein-1 (AP-1), janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3), and inflammatory cytokine expression in the cerulein-stimulated pancreatic acinar cells and rat models. The inflammatory events result in development of acute edematous pancreatitis. DHA induces activation of peroxisome proliferator-activated receptor-γ (PPAR-γ) and expression of the PPARγ-target gene, SOD1, and catalase. Since SOD1 and catalase scavenge ROS, DHA inhibits the ROS-mediated activation of inflammatory signaling (PKC-δ, NF-κB, AP-1, JAK2/STAT3) and inflammatory cytokine expression in cerulein-stimulated pancreatic acinar cells and animal models. Antioxidant and anti-inflammatory effects of DHA may be responsible for preventing the development of acute pancreatitis. The bars represent inhibition, while the…

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  Figure 2. Proposed mechanisms of action of docosahexaenoic acid (DHA) in hypertriglyceridemic and hyperlipidemic acute pancreatitis. DHA inhibits triglyceride (TG) and fatty acid (FA) synthesis in the liver. DHA increases lipoprotein lipase (LPL) activity in the extrahepatic tissues and β-oxidation of FA in the liver and skeletal muscles, thereby contributing to the reduction of FA delivery to the liver and reducing plasma TG levels. High amounts of FAs induce pancreatic inflammation and injury. Therefore, the TG-lowering effect of DHA may prevent hypertriglyceridemic acute pancreatitis. On the other hand, a high concentration of DHA increases Ca2+ and activates PKC isoforms (PKC-α, PKC-δ, PKC-ε, and PKC-ζ) in pancreatic acinar cells, which may induce zymogene activation and pancreatic injury associated with hyperlipidemic acute pancreatitis. In addition, PKC activates NF-κB and induces inflammatory cytokine expression in pancreatic acinar cells. The bars represent inhibition, while the arrows represent stimulation.