S-Space Graduate School of Convergence Science and Technology (융합과학기술대학원) Dept. of Molecular and Biopharmaceutical Sciences (분자의학 및 바이오제약학과) Journal Papers (저널논문_분자의학 및 바이오제약학과)
Novel antioxidant ameliorates the fibrosis and inflammation of cerulein-induced chronic pancreatitis in a mouse model
- Yoo, Byung-Moo; Oh, Tae-Young; Kim, Young-Bae; Yeo, Marie; Lee, Jeong-Sang; Surh, Young-Joon; Ahn, Byoung-Ok; Kim, Wook-Hwan; Sohn, Seonghyang; Kim, Jin-Hong; Hahm, Ki-Baik
- Issue Date
- Pancreatology, Vol.5 No.2-3, pp.165-176
- chronic pancreatitis; fibrosis; mice model; cerulein-induced pancreatitis; pancreatic stellate cell; oxidative stress; DA-9601
- 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-κ B 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 α-SMA and type I collagen in cultured pancreatic stellate cells. Conclusions: Oxidative stress was principally involved in the pathogenesis of chronic pancreatitis with fibrosis. Copyright (C) 2005 S. Karger AG, Basel and IAP.
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