Nitroxides prevent exacerbation of indomethacin-induced gastric damage in adjuvant arthritis rats

Hisato Deguchi, Keiji Yasukawa, Toshihide Yamasaki, Fumiya Mito, Yuichi Kinoshita, Tatsuya Naganuma, Suguru Sato, Mayumi Yamato, Kazuhiro Ichikawa, Kiyoshi Sakai, Hideo Utsumi, Ken-Ichi Yamada

Research output: Contribution to journalArticle

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Abstract

Nonsteroidal anti-inflammatory drugs are the drugs of choice in the treatment of rheumatoid arthritis (RA) because of their rapid analgesic effect. However, they induce severe gastric damage in RA patients and animals by a process mediated by reactive oxygen species (ROS). Nitroxides (nitroxyl radicals) are widely used as imaging agents and antioxidants to explore the role of ROS generation in the pathogenesis of disease. In this study, the effectiveness of the newly synthesized nitroxides 8-aza-7,7,9,9-tetramethyl-1,4- dioxaspiro[4.5]undecan-8-oxyl (compound 1) and 4-oxo-2,2,6,6- tetraethylpiperidine-1-oxyl (compound 2) in the prevention of gastric ulcers in adjuvant arthritis rats treated with indomethacin was evaluated by monitoring the reaction of reactive oxygen species in gastric tissue with Overhauser-enhanced magnetic resonance imaging (OMRI). Pretreatment with all tested nitroxides suppressed the ulcers induced by indomethacin treatment in arthritic rats. OMRI using compounds 1 and 2 as well as 4-hydroxy-2,2,6,6- tetramethylpiperidine-1-oxyl (TEMPOL) demonstrated a redox imbalance in the stomach of these rats. Lipid peroxide and interleukin (IL)-1β levels in the gastric mucosa were significantly suppressed by compound 1 and TEMPOL, whereas CINC/gro, a member of the IL-8 family, was significantly suppressed by compound 1 only. These results suggest that the preventive effects of nitroxides on gastric ulcers may operate by different mechanisms.

Original languageEnglish
Pages (from-to)1799-1805
Number of pages7
JournalFree Radical Biology and Medicine
Volume51
Issue number9
DOIs
Publication statusPublished - Nov 1 2011

Fingerprint

Experimental Arthritis
Indomethacin
Rats
Reactive Oxygen Species
Stomach
Magnetic resonance
Stomach Ulcer
Imaging techniques
Rheumatoid Arthritis
Magnetic Resonance Imaging
Lipid Peroxides
Gastric Mucosa
Interleukin-8
Interleukin-1
Pharmaceutical Preparations
Ulcer
Oxidation-Reduction
Arthritis
Analgesics
Animals

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Physiology (medical)

Cite this

Nitroxides prevent exacerbation of indomethacin-induced gastric damage in adjuvant arthritis rats. / Deguchi, Hisato; Yasukawa, Keiji; Yamasaki, Toshihide; Mito, Fumiya; Kinoshita, Yuichi; Naganuma, Tatsuya; Sato, Suguru; Yamato, Mayumi; Ichikawa, Kazuhiro; Sakai, Kiyoshi; Utsumi, Hideo; Yamada, Ken-Ichi.

In: Free Radical Biology and Medicine, Vol. 51, No. 9, 01.11.2011, p. 1799-1805.

Research output: Contribution to journalArticle

Deguchi, H, Yasukawa, K, Yamasaki, T, Mito, F, Kinoshita, Y, Naganuma, T, Sato, S, Yamato, M, Ichikawa, K, Sakai, K, Utsumi, H & Yamada, K-I 2011, 'Nitroxides prevent exacerbation of indomethacin-induced gastric damage in adjuvant arthritis rats', Free Radical Biology and Medicine, vol. 51, no. 9, pp. 1799-1805. https://doi.org/10.1016/j.freeradbiomed.2011.08.010
Deguchi, Hisato ; Yasukawa, Keiji ; Yamasaki, Toshihide ; Mito, Fumiya ; Kinoshita, Yuichi ; Naganuma, Tatsuya ; Sato, Suguru ; Yamato, Mayumi ; Ichikawa, Kazuhiro ; Sakai, Kiyoshi ; Utsumi, Hideo ; Yamada, Ken-Ichi. / Nitroxides prevent exacerbation of indomethacin-induced gastric damage in adjuvant arthritis rats. In: Free Radical Biology and Medicine. 2011 ; Vol. 51, No. 9. pp. 1799-1805.
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