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Celecoxib, a selective cyclooxygenase-2 inhibitor, aggravates radiation-induced intestinal damage in mice KCI 등재

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충북대학교 동물의학연구소 (Research Institute of Veterinary Medicine, Chungbuk National University)
초록

Celecoxib, a cyclooxygenase (COX)-2 selective inhibitor, was approved as a non-steroidal anti-inflammatory drug (NSAID), and this therapeutic application has been expanded to several other diseases, including colon cancer. Notably, a treatment strategy combining the use of celecoxib and radiation therapy has been employed for improving the control of local cancers. In this study, we examined the effect of celecoxib on irradiation-induced intestinal damage. The twenty four mice (BALB/c) were divided into four groups; 1) sham-irradiated control group, 2) celecoxib-treated group, 3) irradiated group, and 4) celecoxib-treated irradiation group. Mice were orally administered celecoxib at a dose of 25 mg/kg in a 0.1 mL volume, daily for 4 days after irradiation exposure (10 Gy). Then, histological examinations of the jejunal villous height, crypt survival, and crypt size were performed. The expression of COX-2 after administration of celecoxib in irradiated mice was examined by employing immunohistochemistry, Western blotting, and qPCR analysis. The jejunal villi height and the crypt survival were reduced in the irradiation group compared with the sham-irradiated group. Celecoxib treatment in irradiation mice even more decreased those indicators. Crypt size was increased in the radiation group compared to the sham-irradiated control group, whereas the size was decreased in the celecoxibtreated irradiation group compared with the group exposed to the radiation injury. COX-2 expression was detected in the crypt of the small intestine, and COX-2 expression was increased in the crypt lesion following radiation exposure. However, COX-2 expression was reduced in the celecoxib-treated irradiation group. Therefore, in the present study, we confirmed that celecoxib treatment after irradiation aggravated the irradiation-induced intestinal damage. These results suggest that a caution need to be administered when celecoxib treatment is performed in combination with radiation therapy for cancer treatment.

목차
Introduction
Materials and Methods
    Animal maintenance and study schedule
    Immunohistochemistry
    Western blotting
    Quantitative reverse transcription-polymerase chainreaction (qRT-PCR) analysis
    Statistical analysis
Results
    Effect of celecoxib on intestinal morphological changesin irradiated mice
    Effect of celecoxib on COX-2 expression in theintestine of irradiated mice
Discussion
References
저자
  • Sueun Lee(Herbal Medicine Resources Research Center, Korea Institute of Oriental Medicine)
  • Jin Mi Chun(Herbal Medicine Resources Research Center, Korea Institute of Oriental Medicine)
  • Ji Hye Lee(Herbal Medicine Resources Research Center, Korea Institute of Oriental Medicine)
  • Yun-Soo Seo(Herbal Medicine Resources Research Center, Korea Institute of Oriental Medicine)
  • Jun Hong Park(Herbal Medicine Resources Research Center, Korea Institute of Oriental Medicine)
  • Hae-June Lee(Division of Radiation Effects, Korea Institute of Radiological and Medical Sciences)
  • Changjong Moon(College of Veterinary Medicine and BK21 Plus Project Team, Chonnam National University)
  • Sung-Ho Kim(College of Veterinary Medicine and BK21 Plus Project Team, Chonnam National University) Corresponding author
  • Joong-Sun Kim(Herbal Medicine Resources Research Center, Korea Institute of Oriental Medicine) Corresponding author