Protective effect and mechanism of amifostine on intestinal acute radiation sickness
ZHAO Zhiwei1,2, CUI Yu2,WANG Limei2, SHAN Yajun2,TANG Hongwei3, CONG Yuwen2
1.Graduate School,Xuzhou Medical College, Xuzhou 221000, China; 2.Institute of Radiation Medicine,Academy of Military Medical Science,Beijing 100850,China; 3.Department of Gastroenterology,The General Hospital of Chinese People’s Armed Police Forces, Beijing100039,China
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.
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.
[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.
[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.
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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[11]
Sangiorgi E, Capecchi M R. Bmi1 is expressed in vivo in intestinal stem cells[J]. Nat Genet,2008, 40(7):915-920.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.
[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.