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Novel antioxidant ameliorates the fibrosis and inflammation of cerulein-induced chronic pancreatitis in a mouse model.

Authors
Yoo, BM; Oh, TY; Kim, YB; Yeo, M; Lee, JS; Surh, YJ; Ahn, BO; Kim, WH; Sohn, S; Kim, JH; Hahm, KB
Citation
Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.], 5(2-3):165-176, 2005
Journal Title
Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]
ISSN
1424-39031424-3911
Abstract
BACKGROUND/AIM: Oxygen free radicals (OFRs) mediate an important step in the initiation of experimental acute pancreatitis and several clinical findings suggested the possible contribution of OFRs to the pathogenesis of pancreatic fibrosis. So far, there are no studies which reporting potential role of OFRs in development of chronic pancreatitis with the prevention with antioxidants. This study was aimed to establish the mice model of chronic fibrosing pancreatitis and to prove the involvement of OFRs in chronic pancreatitis with fibrosis.



METHODS: Repeated intraperitoneal cerulein injection was performed to induce chronic pancreatitis in mice. Histological changes in the pancreas were examined, and markers for oxidative stress were measured in the pancreatic tissue and serum of the mice. DA-9601, a phytochemical possessing anti-inflammatory and antioxidative action, was given together with cerulein to the mice.



RESULTS: Repeated intraperitoneal injection of cerulein provoked significant severity of chronic fibrosing pancreatitis after 5 weeks. After treatment of DA-9601, the extents of pancreatic fibrosis were statistically significantly decreased in accordance with lessened pancreatic inflammations. The NF-kappaB binding activities were increased in chronic pancreatitis, which were significantly attenuated after DA-9601 treatment. The levels of myeloperoxidase and iNOS activities were also significantly decreased in DA-9601-treated group compared to the pancreatitis only group. Cytoprotective proteins such as heat shock protein-70 (HSP) and metallothionein were significantly increased in the DA-9601-treated group. DA-9601 decreased the expressions of alpha-SMA and type I collagen in cultured pancreatic stellate cells.



CONCLUSIONS: Oxidative stress was principally involved in the pathogenesis of chronic pancreatitis with fibrosis.
MeSH terms
AnimalsAntioxidants/pharmacology*Artemisia*CaeruleinCells, CulturedChronic DiseaseDisease Models, AnimalFibrosisFree Radicals/metabolismMaleMiceMice, Inbred ICROxidative Stress/drug effectsPancreatitis/chemically inducedPancreatitis/drug therapy*Pancreatitis/metabolismPancreatitis/pathology*Plant Extracts/pharmacology*
DOI
10.1159/000085268
PMID
15849487
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Gastroenterology
Journal Papers > School of Medicine / Graduate School of Medicine > Pathology
Journal Papers > Research Organization > Genomic Research Center for Gastroenterology
Journal Papers > School of Medicine / Graduate School of Medicine > Surgery
Journal Papers > School of Medicine / Graduate School of Medicine > Microbiology
AJOU Authors
유, 병무김, 영배여, 말희김, 욱환손, 성향김, 진홍함, 기백
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