Docosahexaenoic Acid Inhibits Expression of Fibrotic Mediators in Mice With Chronic Pancreatitis

Lee, Sle; Jeong, Yoo Kyung; Lim, Joo Weon; Kim, Hyeyoung

Abstract

BACKGROUND
Chronic pancreatitis (CP) is an irreversible progressive disease that destroys exocrine parenchyma, which are replaced by fibrous tissue. As pancreatic fibrosis is a key feature of CP, reducing fibrotic protein content in the pancreas is crucial for preventing CP. Studies suggest that NF-ÎºB facilitates the expression of fibrotic mediators in pancreas and protein kinase C-Î´ (PKC-Î´) regulates NF-ÎºB activation in stimulated pancreatic acinar cells. Docosahexaenoic acid (DHA) is an omega-3 fatty acid having anti-inflammatory and anti-fibrotic effects. It has been shown to inhibit NF-ÎºB activity in cerulein-stimulated pancreatic acinar cells which is a cellular model of CP. In the present study, we investigated if DHA inhibits expression of fibrotic mediators by reducing PKC-Î´ and NF-ÎºB expression in mouse pancreatic tissues with CP.
METHODS
For six weeks, mice were weekly induced for acute pancreatitis to develop CP. Furthermore, acute pancreatitis was induced by hourly intraperitoneal injections of cerulein (50 Î¼g/kg Ã— 7). Mice were administered DHA (10 Î¼M) via drinking water before and after CP induction.
RESULTS
Cerulein-induced pancreatic damages like decreased pancreatic weight/total body weight, leukocyte infiltration, necrosis of acinar cells, and vacuolization were found to be inhibited by DHA. Additionally, DHA inhibited cerulein-induced fibrotic mediators like alpha-smooth muscle actin and fibronectin in pancreas. DHA reduced expression of PKC-Î´ and NF-ÎºB p65 in pancreatic tissues of cerulein-treated mice.
CONCLUSIONS
DHA may be beneficial in preventing CP by suppressing pancreatic expression of fibrotic mediators.