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Attenuation of Gastric Mucosal Inflammation Induced by Aspirin Through Inhibition of Selective Type III Phospshodiesterase in Rats

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Abstract

Cilostazol, a selective type III phosphodiesterase inhibitor, is widely used for treatment of ischemic symptoms of peripheral vascular disease. Recent studies have reported that the mechanism of cilostazol is related to suppression of pro-inflammatory cytokine production and improvement of local microcirculation disturbances. The activation of inflammatory cells and pro-inflammatory cytokine production play critical roles in the pathogenesis of aspirin-induced gastric irritation. The aim of the present study was to determine whether cilostazol can ameliorate aspirin-induced gastric mucosal lesions in rats, reduce neutrophil accumulation, and reduce the production of pro-inflammatory cytokines. Gastric lesions were produced by oral gavage of aspirin (200 mg/kg) and HCl (0.15 N, 8.0 ml/kg). Cilostazol (1–10 mg/kg, IP) was injected 30 min before aspirin administration. Also, we measured the gastric mucosal concentrations of myeloperoxidase and interleukin-1 β, tumor necrosis factor-α, and cytokine-induced neutrophil chemoattractants-1, as an index of neutrophil accumulation, and the pro-inflammatory cytokines. Cilostazol ameliorated the gastric mucosal lesions induced by aspirin administration (P < 0.01). The gastric contents of myeloperoxidase and pro-inflammatory cytokines were all increased after aspirin administration and significantly reduced by cilostazol treatment. In this study, we demonstrated that a selective type III phosphodiesterase inhibitor, cilostazol, reduced aspirin-induced gastric inflammation and damage via suppression of the production of proinflammatory cytokines. Cilostazol may be useful for preventing gastric mucosal lesions induced by aspirin.

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Acknowledgment

The authors wish to express their thanks to Otsuka Pharmaceutical Co., Ltd., Tokyo, for the gift of cilostazol

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Authors and Affiliations

  1. Department of Gastroenterology, Akita University of Medicine, 1-1-1, Hondo, Akita City, 010-8543, Akita, Japan

    Masaru Odashima*, Michiro Otaka*, Reina Ohba*, Mario Jin, Isao Wada, Youhei Horikawa, Tamotsu Matsuhashi, Natsumi Hatakeyama, Jinko Oyake & Sumio Watanabe

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  1. Masaru Odashima*
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  2. Michiro Otaka*
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  3. Reina Ohba*
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  4. Mario Jin
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  5. Isao Wada
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  6. Youhei Horikawa
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  7. Tamotsu Matsuhashi
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  8. Natsumi Hatakeyama
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  9. Jinko Oyake
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  10. Sumio Watanabe
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Correspondence to Masaru Odashima*.

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*These authors contributed equally to this work.

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Odashima*, M., Otaka*, M., Ohba*, R. et al. Attenuation of Gastric Mucosal Inflammation Induced by Aspirin Through Inhibition of Selective Type III Phospshodiesterase in Rats. Dig Dis Sci 52, 1355–1359 (2007). https://doi.org/10.1007/s10620-006-9553-y

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  • DOI: https://doi.org/10.1007/s10620-006-9553-y

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