Novel antioxidant ameliorates the fibrosis and inflammation of cerulein-induced chronic pancreatitis in a mouse model.
OBJECTIVE
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.
Yoo
Byung-Moo
BM
Genome Research Center for Gastroenterology, Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea.
Oh
Tae-Young
TY
Kim
Young-Bae
YB
Yeo
Marie
M
Lee
Jeong-Sang
JS
Surh
Young Joon
YJ
Ahn
Byoung-Ok
BO
Kim
Wook-Hwan
WH
Sohn
Seonghyang
S
Kim
Jin-Hong
JH
Hahm
Ki-Baik
KB
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D019306:Artemisia; D002478:Cells, Cultured; D002108:Ceruletide; D002908:Chronic Disease; D004195:Disease Models, Animal; D005355:Fibrosis; D005609:Free Radicals / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D018384:Oxidative Stress / Q000187:drug effects; D010195:Pancreatitis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D010936:Plant Extracts / Q000494:pharmacology*
D000975:Antioxidants; C116959:DA 9601; D005609:Free Radicals; D010936:Plant Extracts; D002108:Ceruletide