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

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)606-616
Number of pages11
JournalJournal of Gastroenterology and Hepatology (Australia)
Volume17
Issue number5
DOIs
Publication statusPublished - 2002

Fingerprint

Xanthine Oxidase
Chronic Pancreatitis
Lithostathine
Reactive Oxygen Species
Tungsten
Diet
Messenger RNA
DNA Damage
Superoxide Dismutase
Deoxyguanosine
Wounds and Injuries
Oxidants
Free Radicals
Glutathione
Fibrosis
Oxygen
8-oxo-7-hydrodeoxyguanosine
hydroxide ion

Keywords

  • 8-hydroxy-deoxyguanosine
  • Chronic pancreatitis
  • Glutathione
  • Lithostathine
  • Superoxide dismutase
  • Xanthine oxidase

ASJC Scopus subject areas

  • Gastroenterology
  • Hepatology

Cite this

Xanthine oxidase-derived oxygen radicals play significant roles in the development of chronic pancreatitis in WBN/Kob rats. / Zeki, Shigeyuki; Miura, Soichiro; Suzuki, Hidekazu; Watanabe, Naoyuki; Adachi, Masayuki; Yokoyama, Hirokazu; Horie, Yoshinori; Saito, Hidetsugu; Kato, Shinzo; Ishii, Hiromasa.

In: Journal of Gastroenterology and Hepatology (Australia), Vol. 17, No. 5, 2002, p. 606-616.

Research output: Contribution to journalArticle

Zeki, Shigeyuki ; Miura, Soichiro ; Suzuki, Hidekazu ; Watanabe, Naoyuki ; Adachi, Masayuki ; Yokoyama, Hirokazu ; Horie, Yoshinori ; Saito, Hidetsugu ; Kato, Shinzo ; Ishii, Hiromasa. / Xanthine oxidase-derived oxygen radicals play significant roles in the development of chronic pancreatitis in WBN/Kob rats. In: Journal of Gastroenterology and Hepatology (Australia). 2002 ; Vol. 17, No. 5. pp. 606-616.
@article{a6ef98195c964091b8d12cda1a92820d,
title = "Xanthine oxidase-derived oxygen radicals play significant roles in the development of chronic pancreatitis in WBN/Kob rats",
abstract = "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.",
keywords = "8-hydroxy-deoxyguanosine, Chronic pancreatitis, Glutathione, Lithostathine, Superoxide dismutase, Xanthine oxidase",
author = "Shigeyuki Zeki and Soichiro Miura and Hidekazu Suzuki and Naoyuki Watanabe and Masayuki Adachi and Hirokazu Yokoyama and Yoshinori Horie and Hidetsugu Saito and Shinzo Kato and Hiromasa Ishii",
year = "2002",
doi = "10.1046/j.1440-1746.2002.02733.x",
language = "English",
volume = "17",
pages = "606--616",
journal = "Journal of Gastroenterology and Hepatology (Australia)",
issn = "0815-9319",
publisher = "Wiley-Blackwell",
number = "5",

}

TY - JOUR

T1 - Xanthine oxidase-derived oxygen radicals play significant roles in the development of chronic pancreatitis in WBN/Kob rats

AU - Zeki, Shigeyuki

AU - Miura, Soichiro

AU - Suzuki, Hidekazu

AU - Watanabe, Naoyuki

AU - Adachi, Masayuki

AU - Yokoyama, Hirokazu

AU - Horie, Yoshinori

AU - Saito, Hidetsugu

AU - Kato, Shinzo

AU - Ishii, Hiromasa

PY - 2002

Y1 - 2002

N2 - 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.

AB - 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.

KW - 8-hydroxy-deoxyguanosine

KW - Chronic pancreatitis

KW - Glutathione

KW - Lithostathine

KW - Superoxide dismutase

KW - Xanthine oxidase

UR - http://www.scopus.com/inward/record.url?scp=0036301858&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036301858&partnerID=8YFLogxK

U2 - 10.1046/j.1440-1746.2002.02733.x

DO - 10.1046/j.1440-1746.2002.02733.x

M3 - Article

VL - 17

SP - 606

EP - 616

JO - Journal of Gastroenterology and Hepatology (Australia)

JF - Journal of Gastroenterology and Hepatology (Australia)

SN - 0815-9319

IS - 5

ER -