Pancreas · 2014
Protective effects of fucoidan, a P- and L-selectin inhibitor, in murine acute pancreatitis.
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Carvalho Ana C S, Sousa Rhamon B, Franco Álvaro Xavier, Costa José Victor Gomes, Neves Luara Manuela, Ribeiro Ronaldo A, Sutton Robert, Criddle David N, Soares Pedro M G, de Souza Marcellus H L P
Аннотация
OBJECTIVE: The objective of this study was to investigate the potential protective effects of fucoidan, an L- and P-selectin modulator, in 2 murine models of acute pancreatitis.
METHODS: Acute pancreatitis was induced in mice either by the retrograde infusion of taurolithocholic acid sulfate into the pancreatic duct or by intraperitoneal injections of cerulein (50 μg/kg per hour). The experimental groups received fucoidan (25 mg/kg, intravenously) before pancreatitis induction, whereas control groups received only saline. After 24 hours, serum amylase, lipase, interleukin 1β (IL-1β), tumor necrosis factor α (TNF-α), and nitrite were measured. In addition, myeloperoxidase (MPO) activity (lung and pancreas) and histological assessment (pancreas) were determined.
RESULTS: Serum amylase, lipase, nitrite, TNF-α, and IL-1β, and pancreatic and lung MPO were increased in both taurolithocholic acid sulfate and cerulein acute pancreatitis compared with the respective control groups. Fucoidan significantly decreased the augmented levels of amylase, lipase, pancreatic and lung MPO, TNF-α, IL-1β, and nitrite in both models. Pancreas histological changes observed in both acute pancreatitis models were significantly attenuated by fucoidan.
CONCLUSIONS: Fucoidan reduced the severity of acute pancreatitis in mice by decreasing neutrophil infiltration and systemic inflammation, suggesting that modulation of selectins may constitute a promising therapeutic approach.
METHODS: Acute pancreatitis was induced in mice either by the retrograde infusion of taurolithocholic acid sulfate into the pancreatic duct or by intraperitoneal injections of cerulein (50 μg/kg per hour). The experimental groups received fucoidan (25 mg/kg, intravenously) before pancreatitis induction, whereas control groups received only saline. After 24 hours, serum amylase, lipase, interleukin 1β (IL-1β), tumor necrosis factor α (TNF-α), and nitrite were measured. In addition, myeloperoxidase (MPO) activity (lung and pancreas) and histological assessment (pancreas) were determined.
RESULTS: Serum amylase, lipase, nitrite, TNF-α, and IL-1β, and pancreatic and lung MPO were increased in both taurolithocholic acid sulfate and cerulein acute pancreatitis compared with the respective control groups. Fucoidan significantly decreased the augmented levels of amylase, lipase, pancreatic and lung MPO, TNF-α, IL-1β, and nitrite in both models. Pancreas histological changes observed in both acute pancreatitis models were significantly attenuated by fucoidan.
CONCLUSIONS: Fucoidan reduced the severity of acute pancreatitis in mice by decreasing neutrophil infiltration and systemic inflammation, suggesting that modulation of selectins may constitute a promising therapeutic approach.