Docosahexaenoic Acid Inhibits Cerulein-Induced Acute Pancreatitis in Rats.

Yoo Jeong,Joo Lim,Sle Lee,Hyeyoung Kim

doi:10.3390/nu9070744

Abstract

Oxidative stress is an important regulator in the pathogenesis of acute pancreatitis (AP). Reactive oxygen species induce activation of inflammatory cascades, inflammatory cell recruitment, and tissue damage. NF-κB regulates inflammatory cytokine gene expression, which induces an acute, edematous form of pancreatitis. Protein kinase C δ (PKCδ) activates NF-κB as shown in a mouse model of cerulein-induced AP. Docosahexaenoic acid (DHA), an ω-3 fatty acid, exerts anti-inflammatory and antioxidant effects in various cells and tissues. This study investigated whether DHA inhibits cerulein-induced AP in rats by assessing pancreatic edema, myeloperoxidase activity, levels of lipid peroxide and IL-6, activation of NF-κB and PKCδ, and by histologic observation. AP was induced by intraperitoneal injection (i.p.) of cerulein (50 μg/kg) every hour for 7 h. DHA (13 mg/kg) was administered i.p. for three days before AP induction. Pretreatment with DHA reduced cerulein-induced activation of NF-κB, PKCδ, and IL-6 in pancreatic tissues of rats. DHA suppressed pancreatic edema and decreased the abundance of lipid peroxide, myeloperoxidase activity, and inflammatory cell infiltration into the pancreatic tissues of cerulein-stimulated rats. Therefore, DHA may help prevent the development of pancreatitis by suppressing the activation of NF-κB and PKCδ, expression of IL-6, and oxidative damage to the pancreas.

Highlights

Acute pancreatitis (AP) is an inflammatory disease associated with abnormal activation and release of digestive enzymes to the pancreas, resulting in auto-digestion of the pancreas and multiple organ dysfunction
We have previously shown that cerulein-induced activation of NADPH oxidase produces high levels of Reactive oxygen species (ROS), which activates the oxidant-sensitive transcription factor NF-κB and induces the expression of IL-6 in pancreatic acinar cells [19]
We examined the anti-inflammatory effect of Docosahexaenoic acid (DHA), on cerulein-induced AP in rats, by assessing pancreatic edema, the abundance of lipid peroxide (LPO), activity of myeloperoxidase (MPO), expression of IL-6, activation of NF-κB and Protein kinase C δ (PKCδ), and histologic changes

Summary

Introduction

Acute pancreatitis (AP) is an inflammatory disease associated with abnormal activation and release of digestive enzymes to the pancreas, resulting in auto-digestion of the pancreas and multiple organ dysfunction. It is associated with increased production of cytokines, leading to deleterious local and systemic effects [1,2,3]. Cerulein-induced pancreatitis is one of the best-characterized and widely used experimental animal models of pancreatitis. Studies, using experimental models of pancreatitis, indicate that pancreatic oxidative stress occurs during the early stage in the induction of AP [8]

Objectives

Methods

Results

Conclusion