Abstract
Acute pancreatitis refers to the sudden inflammation of the pancreas. It is associated with premature activation and release of digestive enzymes into the pancreatic interstitium and systemic circulation, resulting in pancreatic tissue autodigestion and multiple organ dysfunction, as well as with increased cytokine production, ultimately leading to deleterious local and systemic effects. Although mechanisms involved in pathogenesis of acute pancreatitis have not been completely elucidated, oxidative stress is regarded as a major risk factor. In human acute pancreatitis, lipid peroxide levels in pancreatic tissues increase. Docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid (C22:6n-3), exerts anti-inflammatory and antioxidant effects on various cells. Previous studies have shown that DHA activates peroxisome proliferator-activated receptor-γ and induces catalase, which inhibits oxidative stress-mediated inflammatory signaling required for cytokine expression in experimental acute pancreatitis using cerulein. Cerulein, a cholecystokinin analog, induces intra-acinar activation of trypsinogen in the pancreas, which results in human acute pancreatitis-like symptoms. Therefore, DHA supplementation may be beneficial for preventing or inhibiting acute pancreatitis development. Since DHA reduces serum triglyceride levels, addition of DHA to lipid-lowering drugs like statins has been investigated to reduce hypertriglyceridemic acute pancreatitis. However, high DHA concentrations increase cytosolic Ca2+, which activates protein kinase C and may induce hyperlipidemic acute pancreatitis. In this review, effect of DHA on cerulein-induced and hypertriglyceridemic acute pancreatitis has been discussed. The relation of high concentration of DHA to hyperlipidemic acute pancreatitis has been included.
Highlights
Acute pancreatitis is an inflammatory disease of the pancreas, which may result in multiple organ dysfunction and increased cytokine release [1,2]
Docosahexaenoic acid (DHA) induces the expression of peroxisome proliferator-activated receptor-γ (PPAR-γ)-target gene, SOD1, and catalase, thereby inhibiting reactive oxygen species (ROS)-mediated activation of inflammatory signaling (PKC-δ, nuclear factor-κB (NF-κB), activator protein-1 (AP-1), JAK2/STAT3) and inflammatory cytokine expression in cerulein-stimulated pancreatic acinar cells and rat models
DHA-induced activation of PPAR-γ and catalase expression may be responsible for the anti-inflammatory effects of DHA in cerulein-induced acute pancreatitis
Summary
Acute pancreatitis is an inflammatory disease of the pancreas, which may result in multiple organ dysfunction and increased cytokine release [1,2]. DHA inhibited PKC-δ activation and increased the expression of antioxidant enzyme SOD1 in pancreatic tissues of cerulein-treated rats [74]. These results suggested that DHA may be beneficial for preventing the development of pancreatitis by suppressing the activation of PKC-δ and NF-κB, and inhibiting the expression of inflammatory cytokines. DHA activates PPAR-γ and induces the expression of PPAR-γ-target gene, SOD1 and catalase, thereby inhibiting ROS-mediated activation of PKC-δ, NF-κB, AP-1, JAK2/STAT3, and inflammatory cytokine expression, in the in vitro cerulein-stimulated pancreatic acinar cells and in vivo rat models (Figure 1). HHyyppeerrttrriiggllyycceerriiddeemmiiaa wwiitthh sseerruummTTGGlelevveelsls≥≥550000mmgg//ddLL ((≥≥55..6655 mmmmooll//LL),),ininccrreeaasseesstthhee rriisskk ooff aaccuuttee ppaannccrreeaattiittiiss[7[755].].TThheererefoforer,el,olwowereirnigngTGTGlevleevlserlsedruedceuscethsethrieskriosfkpoafnpcraenactriteias.tiBtios.thBgoethnegtiecnaentidc saencdonsdeacroynddiasroyrddeirssoorfdleirpsoporfotleiipnompreottaebinolismmetaarbeoalisssmociaatreed awssitohcihaytepdertwriigtlhycheryipdeermtriicgplyacnecrriedaetmitiisc. IFn-κaBdadnitdioin,dPuKceCs iancfltiavmatmesaNtoFry-κcBytaonkdiniendexupcreessisnioflnaminmpaatnocrryeactyitcoakciinnearexcpelrless. sTiohne binarpsarnecprreeasteicntaicninhaibritcieolnls,.wThielebtahres arerprorwessenretpinrehsiebnitiostnim, wuhlailteiotnh.e arrows represent stimulation
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