Radiation Oncology Journal

  • 제28권3호
  • /
  • Pages.141-146
  • /
  • 2010
  • /
  • 2234-1900(pISSN)
  • /
  • 2234-3156(eISSN)
대한방사선종양학회 (The Korean Society for Radiation Oncology)
권호 표지
DOI QR코드

DOI QR Code

방사선에 의한 장점막 손상에 대한 5-Androstenediol의 보호효과

Protective Effects of 5-Androstendiol (5-AED) on Radiation-induced Intestinal Injury

  • 김중선 (한국원자력의학원 실험병리연구실) ;
  • 이승숙 (한국원자력의학원 실험병리연구실) ;
  • 장원석 (한국원자력의학원 실험병리연구실) ;
  • 이선주 (한국원자력의학원 실험병리연구실) ;
  • 박선후 (한국원자력의학원 실험병리연구실) ;
  • 조수연 (한국원자력의학원 실험병리연구실) ;
  • 문창종 (전남대학교 수의과대학 수의해부학실험실) ;
  • 김성호 (전남대학교 수의과대학 수의해부학실험실) ;
  • 김미숙 (한국원자력의학원 방사선종양학과)
  • Kim, Joong-Sun (Laboratory of Experimental Pathology, Korea Institute of Radiological & Medical Sciences) ;
  • Lee, Seung-Sook (Laboratory of Experimental Pathology, Korea Institute of Radiological & Medical Sciences) ;
  • Jang, Won-Suk (Laboratory of Experimental Pathology, Korea Institute of Radiological & Medical Sciences) ;
  • Lee, Sun-Joo (Laboratory of Experimental Pathology, Korea Institute of Radiological & Medical Sciences) ;
  • Park, Sun-Hoo (Laboratory of Experimental Pathology, Korea Institute of Radiological & Medical Sciences) ;
  • Cho, Soo-Youn (Laboratory of Experimental Pathology, Korea Institute of Radiological & Medical Sciences) ;
  • Moon, Chang-Jong (Department of Veterinary Anatomy, Chonnam National University College of Veterinary Medicine) ;
  • Kim, Sung-Ho (Department of Veterinary Anatomy, Chonnam National University College of Veterinary Medicine) ;
  • Kim, Mi-Sook (Department of Radiation Oncology, Korea Institute of Radiology & Medical Sciences)
  • 투고 : 2010.04.13
  • 심사 : 2010.07.01
  • 발행 : 2010.09.30
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

목 적: 본 연구에서는 방사선에 의한 장점막 손상에 대한 5-androstendiol (5-AED)의 장점막 보호효과 여부를 마우스 위장관 조직에서 평가하여 방사선 보호제로서의 적용가능성을 모색하고자 하였다. 대상 및 방법: 30마리의 C3H/HeN 마우스를 대조군, 방사선 조사군, 방사선 조사 전 5-AED 처리군으로 나누어, 5 Gy와 10 Gy 전신방사선 조사하였다. 5-AED는 방사선 조사 24시간 전에 체중 당 50 mg/kg으로 피하 주사하였다. 10 Gy 전신 방사선 조사 후 3.5일에 마우스를 희생하여 공장조직을 채취하여 소장움 생존, 융모의 개수, 융모의 높이, 소장움의 크기, 10개 장상피세포 당 기저층의 길이를 측정하여 장점막 손상정도를 비교 평가하였다. 또한 apoptosis의 발생빈도수는 5 Gy 방사선 조사 후 12시간에 TUNEL 방법으로 검수하였다. 결 과: 10 Gy 방사선조사 전 5-AED 투여군에서, 방사선 조사군과 비교하여, 소장움의 소실이 상대적으로 적고 융모의 높이가 유의성 있게 증가하였다. 5-AED 전처치군에서 소장움의 크기가 방사선 조사군에 비교하여 증가하였고, 10개의 장 상피세포 당 기저층 길이는 5-AED 전처치군에서 감소함을 관찰하여 소장조직의 방사선 손상에 대해 5-AED의 보호효과가 있음을 확인하였다. 방사선 조사 시 증가한 apoptosis에 대해서는 5-AED의 투여가 유의성 있는 감소 효과를 나타내지 못하였다. 결 론: 5-AED 투여는 방사선에 의한 소장점막의 형태학적인 손상변화에 대해 보호효과가 있으며, 이러한 결과는 방사선 조사 전 5-AED 투여가 방사선에 의한 장점막 손상에 대한 보호약물로 활용될 수 있는 가능성을 제시한다.

Purpose: We examined the radioprotective effects of 5-androstendiol (5-AED), a natural hormone produced in the reticularis of the adrenal cortex, as a result of intestinal damage in gamma-irradiated C3H/HeN mice. Materials and Methods: Thirty mice (C3H/HeN) were divided into three groups; 1) non-irradiated control group, 2) irradiated group, and 3) 5-AED-treated group prior to irradiation. Next, 5-AED (50 mg/kg per body weight) was subcutaneously injected 24 hours before irradiation. The mice were whole-body irradiated with 10 Gy for the histological examination of jejunal crypt survival and the determination of the villus morphology including crypt depth, crypt size, number of villi, villus height, and length of basal lamina, as well as 5 Gy for the detection of apoptosis. Results: The 5-AED pre-treated group significantly increased the survival of the jejunal crypt, compared to irradiation controls (p<0.05 vs. irradiation controls at 3.5 days after 10 Gy). The evaluation of morphological changes revealed that the administration of 5-AED reduced the radiation-induced intestinal damages such as villus shortening and increased length of the basal lamina of enterocytes (p<0.05 vs irradiation controls on 3.5 day after 10 Gy, respectively). The administration of 5-AED decreased the radiation-induced apoptosis in the intestinal crypt, with no significant difference between the vehicle and 5-AED at 12 hours after 5 Gy. Conclusion: The results of this study suggest that the administration of 5-AED has a protective effect on intestinal damage induced by $\gamma$-irradiation. In turn, these results suggest that 5-AED could be a useful candidate for radioprotection against intestinal mucosal injury following irradiation.

키워드

참고문헌

  1. Potten CS, Wilson JW, Booth C. Regulation and significance of apoptosis in the stem cells of the gastrointestinal epithelium. Stem Cells 1997;15:82-93 https://doi.org/10.1002/stem.150082
  2. Jagetia GC. Radioprotective potential of plants and herbs against the effects of ionizing radiation. J Clin Biochem Nutr 2007;40:74-81 https://doi.org/10.3164/jcbn.40.74
  3. Monti P, Wysocki J, van der Meeren A, Griffiths NM. The contribution of radiation-induced injury to the gastrointestinal tract in the development of multi-organ dysfunction syndrome or failure. BJR Suppl 2005;27:89-94
  4. Herodin F, Drouet M. Cytokine-based treatment of accidentally irradiated victims and new approaches. Exp Hematol 2005;33:1071-1080 https://doi.org/10.1016/j.exphem.2005.04.007
  5. Whitnall MH, Elliott TB, Harding RA, et al. Androstenediol stimulates myelopoiesis and enhances resistance to infection in gamma-irradiated mice. Int J Immunopharmacol 2000;22:1-14 https://doi.org/10.1016/S0192-0561(99)00059-4
  6. Whitnall MH, Wilhelmsen CL, McKinney L, Miner V, Seed TM, Jackson WE 3rd. Radioprotective efficacy and acute toxicity of 5-androstenediol after subcutaneous or oral administration in mice. Immunopharmacol Immunotoxicol 2002;24:595-626 https://doi.org/10.1081/IPH-120016038
  7. Whitnall MH, Villa V, Seed TM, et al. Molecular specificity of 5-androstenediol as a systemic radioprotectant in mice. Immunopharmacol Immunotoxicol 2005;27:15-32 https://doi.org/10.1081/IPH-51289
  8. Singh VK, Shafran RL, Inal CE, Jackson WE 3rd, Whitnall MH. Effects of whole-body gamma irradiation and 5-androstenediol administration on serum G-CSF. Immunopharmacol Immunotoxicol 2005;27:521-534 https://doi.org/10.1080/08923970500416707
  9. Singh VK, Grace MB, Jacobsen KO, et al. Administration of 5-androstenediol to mice: pharmacokinetics and cytokine gene expression. Exp Mol Pathol 2008;84:178-188 https://doi.org/10.1016/j.yexmp.2007.12.001
  10. Stickney DR, Dowding C, Authier S, et al. 5-androstenediol improves survival in clinically unsupported rhesus monkeys with radiation-induced myelosuppression. Int Immunopharmacol 2007;7:500-505 https://doi.org/10.1016/j.intimp.2006.12.005
  11. Kim SH, Lee HJ, Kim JS, et al. Protective effect of an herbal preparation (HemoHIM) on radiation-induced intestinal injury in mice. J Med Food 2009;12:1353-1358 https://doi.org/10.1089/jmf.2008.1322
  12. Lee HJ, Kim JS, Moon C, Kim JC, Jo SK, Kim SH. Relative biological effectiveness of fast neutrons in a multiorgan assay for apoptosis in mouse. Environ Toxicol 2008;23:233-239 https://doi.org/10.1002/tox.20328
  13. Moon C, Kim SH, Kim JC, et al. Protective effect of phlorotannin components phloroglucinol and eckol on radiationinduced intestinal injury in mice. Phytother Res 2008;22:238-242 https://doi.org/10.1002/ptr.2298
  14. Potten CS, Grant HK. The relationship between ionizing radiation-induced apoptosis and stem cells in the small and large intestine. Br J Cancer 1998;78:993-1003 https://doi.org/10.1038/bjc.1998.618
  15. Booth C, Booth D, Williamson S, Demchyshyn LL, Potten CS. Teduglutide ([Gly2]GLP-2) protects small intestinal stem cells from radiation damage. Cell Prolif 2004;37:385-400 https://doi.org/10.1111/j.1365-2184.2004.00320.x
  16. Driak D, Osterreicher J, Vavrova J, Rehakova Z, Vilasova Z. Morphological changes of rat jejunum after whole body gamma-irradiation and their impact in biodosimetry. Physiol Res 2008;57:475-479
  17. Kudo T, Matsumoto T, Nakamichi I, et al. Recombinant human granulocyte colony-stimulating factor reduces colonic epithelial cell apoptosis and ameliorates murine dextran sulfate sodium-induced colitis. Scand J Gastroenterol 2008;43:689-697 https://doi.org/10.1080/00365520701864627
  18. Hommes DW, Meenan J, Dijkhuizen S, Ten Kate FJ, Tytgat GN, Van Deventer SJ. Efficacy of recombinant granulocyte colony-stimulating factor (rhG-CSF) in experimental colitis. Clin Exp Immunol 1996;106:529-533 https://doi.org/10.1046/j.1365-2249.1996.d01-863.x
  19. Ryu MR, Chung SM, Kay CS, Kim YS, Yoon SC. Radioprotective effects of granulocyte-colony stimulating factor in the jejunal mucosa of mouse. J Korean Soc Ther Radiol Oncol 2001;19:45-52
  20. von Bultzingslowen I, Brennan MT, Spijkervet FK, et al. Growth factors and cytokines in the prevention and treatment of oral and gastrointestinal mucositis. Support Care Cancer 2006;14:519-527 https://doi.org/10.1007/s00520-006-0052-7
  21. Makkonen TA, Minn H, Jekunen A, Vilja P, Tuominen J, Joensuu H. Granulocyte macrophage-colony stimulating factor (GM-CSF) and sucralfate in prevention of radiationinduced mucositis: a prospective randomized study. Int J Radiat Oncol Biol Phys 2000;46:525-534 https://doi.org/10.1016/S0360-3016(99)00452-6
  22. Kim JS, Lee SS, Jeon BS, Jang WS, Moon CJ, Kim SH. Protection of spermatogenesis against gamma rayinduced damage by granulocyte-colony stimulating factor in mice. Andrologia. Forthcoming 2010
  23. Lan X, Qu H, Yao W, Zhang C. Granulocyte-colony stimulating factor inhibits neuronal apoptosis in a rat model of diabetic cerebral ischemia. Tohoku J Exp Med 2008;216:117-126 https://doi.org/10.1620/tjem.216.117