Protective effect and mechanism of amifostine on intestinal acute radiation sickness

ZHAO Zhiwei, CUI Yu,WANG Limei, SHAN Yajun,TANG Hongwei, CONG Yuwen

Medical Journal of the Chinese People Armed Police Forces ›› 2015, Vol. 26 ›› Issue (8) : 797-800.

PDF(2564 KB)
PDF(2564 KB)
Medical Journal of the Chinese People Armed Police Forces ›› 2015, Vol. 26 ›› Issue (8) : 797-800.
ORIGINAL ARTICLES

Protective effect and mechanism of amifostine on intestinal acute radiation sickness

  • ZHAO Zhiwei1,2, CUI Yu2,WANG Limei2, SHAN Yajun2,TANG Hongwei3, CONG Yuwen2
Author information +
History +

Abstract

Objective To study the radioprotection effect and mechanism of amifostine (WR2721) on intestinal acute radiation sickness. Methods Based on the intestinal acute radiation sickness model, C57BL/6J mice were randomly divided into control group and group WR2721. Bone marrow cells from healthy mice were transplanted after 15 Gy 60Co-γ shielded body irradiation. Then the survival rate in 30 d after irradiation, and the number of proliferative crypt cells and the small intestine mucosa situation with micro-cloning survival assay of mouse crypt cells at 3.5d post-irradiation were observed . Results The mice in control group died within 10 days, survival rate in WR2721 administrered group increased to 80%; in the control group and WR2721 drug group, the average number of crypts were 6.1±0.7, 28±1.1, the difference was statistically significant (P<0.0001); in control group and WR2721 administered group, villus heights were(51.48±2.04)μm, (73.29±3.24)μm, the difference was statistically significant (P<0.0001). Conclusions WR2721 has significantly radioprotective effect on intestinal acute radiation sickness by improving the survival rate of mice, promoting crypt cells regeneration and protecting the intestinal mucosa.

Key words

WR2721 / radioprotection / intestinal acute radiation sickness / mechanism

Cite this article

Download Citations
ZHAO Zhiwei, CUI Yu,WANG Limei, SHAN Yajun,TANG Hongwei, CONG Yuwen. Protective effect and mechanism of amifostine on intestinal acute radiation sickness[J]. Medical Journal of the Chinese People Armed Police Forces. 2015, 26(8): 797-800

References

[1] Waselenko J K, MacVittie T J, Blakely W F, et al. Medical management of the acute radiation syndrome:Recommendations of the Strategic National Stockpile Radiation Working Group[J]. Ann Intern Med, 2004,140(1):1037-1051.
[2] Koenig K L, Goans R E, Hatchett R J,et al. Medical treatment of radiological casualties: current concepts[J]. Ann Emerg Med,2005,45(6):643-652.
[3] 艾辉胜, 余长林, 乔建辉, 等. 异基因外周血造血干细胞移植治疗极重度骨髓型和肠型急性放射病的临床报告[J]. 解放军医学杂志,2007,32(4):287-289.
[4] 王丹红,艾辉胜, 乔建辉,等.极重度骨髓型和肠型急性放射病细菌感染的防治[J].解放军医学杂志,2007,5(32):430-432.
[5] Shaw L M,Bonner H S,Brown D Q.Metabolic pathways of WR2721(ethyol,amifostine)in the BALB/c mouse[J].Drug Metab Dispos,1994,22(6):895-902.
[6] Kouvaris J R, Kouloulias V E, Vlahos L J.Amifostine: the first selective-target and broad spectrum radioprotector[J]. Oncologist ,2007,12: 738-747.
[7] Rades D, Fehlauer F, Bajrovic A,et al. Serious adverse effects of amifostine during radiotherapy head and neck cancer patients[J]. Radiother Oncol, 2004,70: 261-264.
[8] Ozdemir C S, Burgazli K M, Bekenozdemir E,et al.The effect of Amifostine (Ethyol) on intestinal anastomosis in rats with radiation enteritis[J]. European Review for Medical and Pharmacological Sciences,2013,17: 1351-1359.
[9] Changying Chen , Li Tian,Mingzhi Zhang ,et al.Protective effect of amifostine on high-dose methotrexate-induced small intestinal mucositis in mice[J]. Dig Dis Sci,2013,58:3134-3143.
[10] Potten CS. A comprehensive study of the radiobiological response of the murine (BDF1) small intestine[J]. Int J Radiat Biol,1990, 58(6):925–973.
[11] Sangiorgi E, Capecchi M R. Bmi1 is expressed in vivo in intestinal stem cells[J]. Nat Genet,2008, 40(7):915-920.
[12] Takeda N, Jain R, LeBoeuf M R, et al. Interconversion between intestinal stem cell populations in distinct niches[J]. Science,2011,334(6061):1420-1424.
[13] Yan K S, Chia L A, Li X, et al. The intestinal stem cell markers Bmi1 and Lgr5 identify two functionally distinct populations[J]. Proc Natl Acad Sci USA,2012, 109(2):466-471.
[14] Eng-Yen Huang, Feng-Sheng Wang,et al. Amifostine alleviates radiation-induced lethal small bowel damage via promotion of 14-3-3σ-mediated nuclear p53 accumulation[J] .Oncotarget,2014,5(20):9756-9769.
[15] GrdinaD J,Nagy B.Tlle effect of 2-ethanethiol(WRl065)on radiation.induced DNA damage and repair and cell progression in V79 cells[J].Br J Cancer,1986,54(6):933-941.
[16] Rebecca J. Ormsby M D. Protection from radiation-induced apoptosis by the radioprotector amifostine (WR-2721) is radiation dose dependent[J]. Cell Biol Toxicol,2014,30(1):55-66.
[17] Paris F, Fuks Z, Kang A, et al. Endothelial apoptosis as the primary lesion initiating intestinal radiation damage in mice[J]. Science,2001,293(5528):293-297.
[18] Takakura N. Role of intimate interactions between endothelial cells and the surrounding accessory cells in the maturation of blood vessels[J]. J Thromb Haemost, 2011, 9 (Suppl. 1):144-150.
[19] Page E E, Deshpande S S, Nelson N S, et al. Prophylactic administration of amifostine protects vessel thickness and luminal diameter in the setting of irradiation[J].Supplement to Plastic and Reconstructive Surgery,2014,4(134):1-2.
[20] Plasswilm L, Hanjalic A, Hoeper J, et al. Microvessel density and endothelial cell proliferation after amifostine (Ethyol) administration in vivo[J]. Anticancer Res,1999,19(5B):4241-4245.
[21] Giannopoulou E, Katsoris P, Parthymou A,et al. Amifostine protects blood vessels from the effects of ionizing radiation[J]. Anticancer Res, 2002,22(5):2821-2826.
[22] Lv W,Zhang M,Zhang Z,et al.Amifostine acts upon mitochondria to stimulate growth of bone marrow and regulate cytokines[J]. Adv Exp Med Biol,2013,789:195-201.
PDF(2564 KB)

Accesses

Citation

Detail

Sections
Recommended

/