Premium
Xanthine oxidase‐derived oxygen radicals play significant roles in the development of chronic pancreatitis in WBN/Kob rats
Author(s) -
ZEKI SHIGEYUKI,
MIURA SOICHIRO,
SUZUKI HIDEKAZU,
WATANABE NAOYUKI,
ADACHI MASAYUKI,
YOKOYAMA HIROKAZU,
HORIE YOSHINORI,
SAITO HIDETSUGU,
KATO SHINZO,
ISHII HIROMASA
Publication year - 2002
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1046/j.1440-1746.2002.02733.x
Subject(s) - xanthine oxidase , medicine , pancreatitis , malondialdehyde , endocrinology , superoxide dismutase , glutathione , oxidative stress , biochemistry , chemistry , enzyme
Background:Although oxygen‐derived free radicals are known to play a role in cell injury and DNA alterations, the role of active oxidants in chronic pancreatitis has not been fully elucidated. Using WBN/Kob rats, which spontaneously develop chronic pancreatitis‐like lesions, we investigated whether xanthine oxidase (XOD)‐derived oxygen radicals are involved in pancreatic tissue injury.Methods:WBN/Kob rats were fed a control or a tungsten diet. The latter depletes XOD activity. Histologic al changes, glutathione (GSH) content and XOD and superoxide dismutase (SOD) activities were determined in pancreatic tissue. Pancreatic 8‐hydroxy‐deoxyguanosine (8‐OH‐dG) levels and lithostathine mRNA were also examined.Results:In WBN/Kob rats, parenchymal destruction and fibrosis developed at approximately 12 weeks of age and progressed with each month. The activity of XOD was significantly higher in the early period (8–12 weeks), whereas the levels of GSH and SOD decreased after 16 weeks. Levels of 8‐OH‐dG in WBN/Kob rats were significantly elevated at 16 weeks. Lithostathine mRNA levels started to increase at 8 weeks, but were suppressed at 16 weeks. The tungsten diet significantly attenuated the histological changes in WBN/Kob rats. The increase in pancreatic XOD activity and 8‐OH‐dG content in WBN/Kob rats was significantly inhibited by the tungsten diet and lithostathine mRNA levels remained high at 16 weeks.Conclusion:These results suggest that oxygen radicals generated by XOD play an important role in oxidative DNA damage and the development of chronic pancreatic injury. © 2002 Blackwell Publishing Asia Pty Ltd