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  • [Biochem Biophys Res Commun .] Protective effects of tauroursodeoxycholate against radiation-induced intestinal injury in a mouse model

    2024년 11월호
    [Biochem Biophys Res Commun .] Protective effects of tauroursodeoxycholate against radiation-induced intestinal injury in a mouse model

    KIRAMS, 전남대 / 이정민, 이해준*, 김중선*

  • 출처
    Biochem Biophys Res Commun .
  • 등재일
    2024 Sep 10:724:150226.
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    Abstract
    In patients with high-level radiation exposure, gastrointestinal injury is the main cause of death. Despite the severity of damage to the gastrointestinal tract, no specific therapeutic option is available. Tauroursodeoxycholic acid (TUDCA) is a conjugated form of ursodeoxycholic acid that suppresses endoplasmic reticulum (ER) stress and regulates various cell-signaling pathways. We investigated the effect of TUDCA premedication in alleviating intestinal damage and enhancing the survival of C57BL/6 mice administered a lethal dose (15Gy) of focal abdominal irradiation. TUDCA was administered to mice 1 h before radiation exposure, and reduced apoptosis of the jejunal crypts 12 h after irradiation. At later timepoint (3.5 days), irradiated mice manifested intestinal morphological changes that were detected via histological examination. TUDCA decreased the inflammatory cytokine levels and attenuated the decrease in serum citrulline levels after radiation exposure. Although radiation induced ER stress, TUDCA pretreatment decreased ER stress in the irradiated intestinal cells. The effect of TUDCA indicates the possibility of radiation therapy for cancer in tumor cells. TUDCA did not affect cell proliferation and apoptosis in the intestinal epithelium. TUDCA decreased the invasive ability of the CT26 metastatic colon cancer cell line. Reduced invasion after TUDCA treatment was associated with decreased matrix metalloproteinase (MMP)-7 and MMP-13 expression, which play important roles in invasion and metastasis. This study shows a potential role of TUDCA in protecting against radiation-induced intestinal damage and inhibiting tumor cell migration without any radiation and radiation therapy effect.

     

     

    Affiliations

    Jeongmin Lee 1, Byung-Suk Jeon 2, Sohi Kang 3, Yeonghoon Son 4, Young-Bin Lim 4, Min Ji Bae 5, Wol Soon Jo 5, Chang-Geun Lee 5, In Shik Shin 1, Changjong Moon 1, Hae-June Lee 6, Joong-Sun Kim 7
    1College of Veterinary Medicine and BK21 FOUR Program, Chonnam National University, Gwangju, 61186, Republic of Korea.
    2Toxicological Evaluation Laboratory, Animal and Plant Quarantine Agency, Gimcheon, 39660, Republic of Korea.
    3College of Veterinary Medicine and BK21 FOUR Program, Chonnam National University, Gwangju, 61186, Republic of Korea; Department of Anatomy and Convergence Medical Science, College of Medicine, Institute of Health Sciences, Gyeongsang National University, Jinju, 52727, Republic of Korea.
    4Division of Radiation Biomedical Research, Korea Institute of Radiological & Medical Sciences (KIRAMS), Seoul, 01812, Republic of Korea.
    5Research Center, Dongnam Institute of Radiological & Medical Sciences (DIRAMS), Busan, 46033, Republic of Korea.
    6Research Center, Dongnam Institute of Radiological & Medical Sciences (DIRAMS), Busan, 46033, Republic of Korea. Electronic address: hjlee@kirams.re.kr.
    7College of Veterinary Medicine and BK21 FOUR Program, Chonnam National University, Gwangju, 61186, Republic of Korea. Electronic address: centraline@jnu.ac.kr.

  • 키워드
    Endoplasmic reticulum stress; Intestine; Radiation; Tauroursodeoxycholic acid; Tumor cell invasion.
  • 연구소개
    고용량 방사선에 노출된 마우스에게 Tauroursodeoxycholate (TUDCA)를 이용하여 효과를 확인한 논문입니다. TUDCA는 위장관 내 국소 복부 방사선 조사에서 endoplasmic reticulum (ER) stress를 억제하여 장 손상을 완화하고 생존률을 향상시켰습니다. 또한 전이성 대장암 세포주인 CT26에서 세포의 invasion 능력을 감소 시켰으며, 이와 관련된 주요 생물학적 마커인 MMP7과 MMP13의 발현을 감소 시켰습니다. 이러한 TUDCA는 장 상피의 세포 증식 및 세포 사멸에 영향을 미치지 않으며, TUDCA가 방사선으로 인한 위장관손상에서 유용한 치료제로 이용될 수 있을 것으로 생각됩니다.
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