Xanthine oxidase-derived oxygen radicals play significant roles in the development of chronic pancreatitis in WBN/Kob rats

Shigeyuki Zeki, Soichiro Miura, Hidekazu Suzuki, Naoyuki Watanabe, Masayuki Adachi, Hirokazu Yokoyama, Yoshinori Horie, Hidetsugu Saito, Shinzo Kato, Hiromasa Ishii

研究成果: Article査読

18 被引用数 (Scopus)


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. Histological 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.

ジャーナルJournal of Gastroenterology and Hepatology (Australia)
出版ステータスPublished - 2002

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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