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CV-11974, angiotensin II type I receptor antagonist, reduces the severity of indomethacin-induced rat enteritis

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Abstract

The aim of the present study was to examine the effect of angiotensin II type I receptor antagonist, CV-11974, on indomethacin-induced small intestinal injury in rats. Single administration of indomethacin provoked severe inflammatory lesions in the small intestine. The levels of thiobarbituric acid-reactive substances (TBARS), myeloperoxidase (MPO) activities and cytokine-induced neutrophil chemoattractant-1 (CINC-1) in the intestinal mucosa significantly increased in the indomethacin-treated group compared with the sham group. In addition, the angiotensin II type I receptor was increased in the small intestine after the administration of indomethacin. The development of intestinal lesions in response to indomethacin was prevented by pretreatment with CV-11974 together with significant suppression of the increased level of TBARS, MPO activities and CINC-1. These results indicate that CV-11974 protected against the small intestinal damage elicited by indomethacin, which suggests that angiotensin II/AT1 receptor interaction is involved in the pathogenesis of the intestinal inflammation associated with oxidative stress.

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Authors and Affiliations

  1. Inflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan

    Toshimitsu Okuda, Hiroshi Ichikawa, Yuji Naito & Toshikazu Yoshikawa

  2. Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan

    Norimasa Yoshida

  3. Biomedical Safety Science, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan

    Tomohisa Takagi, Osamu Handa & Satoshi Kokura

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  1. Toshimitsu Okuda
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  2. Norimasa Yoshida
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  3. Tomohisa Takagi
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Correspondence to Norimasa Yoshida.

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Okuda, T., Yoshida, N., Takagi, T. et al. CV-11974, angiotensin II type I receptor antagonist, reduces the severity of indomethacin-induced rat enteritis. Dig Dis Sci 53, 657–663 (2008). https://doi.org/10.1007/s10620-007-9931-0

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  • DOI: https://doi.org/10.1007/s10620-007-9931-0

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