The relationship between the protective effect of amifostine and decreased intercellular adhesion molecule 1 expression.
OBJECTIVE
The objective of our study was to characterize the relationship between the protective effect of amifostine and decreased intercellular adhesion molecule 1 (ICAM-1) expression in early-phase, radiation-induced otitis media and to illustrate the possible mechanism of early-phase radiation-induced otitis media.


METHODS
A comparison study of middle ear tissue was performed by the expression of ICAM-1 and the electron microscope from total 38 guinea pigs. Group A, consisting of 2 pigs, was used as control, and these pigs were not irradiated. Groups B, C, D, and E, consisting of 9 pigs each, were irradiated. Sterile saline was administered intraperitoneally to the pigs in groups B and D before irradiation, and amifostine was administered intraperitoneally as an aqueous solution 30 minutes before irradiation to the pigs in groups C and E. The pigs in groups B and C were killed on the second day after irradiation, and the pigs in groups D and E were killed 30 days after irradiation.


RESULTS
Intercellular adhesion molecule 1 was strongly expressed in the middle ear mucosa of the irradiated pigs after a 45-Gy dose of radiation was administered. Enhanced ICAM-1 expression was accompanied by pathomorphologic changes in the middle ear tissue. Scanning electron microscopy demonstrated the changes. Intercellular adhesion molecule 1 expression in the mucosa of the groups killed on the second day was stronger than that in the mucosa of the groups killed 30 days after irradiation. Amifostine protected the middle ear from radiation injury, and we found that the expression of ICAM-1 in the middle ear mucosa was down-regulated. However, slight expression of ICAM-1 remained 30 days after irradiation.


CONCLUSIONS
Irradiation increased the expression of ICAM-1 in the middle ear mucosa. Amifostine protected the middle ear from early irradiation injury. There was a relationship between oxygen free radicals derived from irradiation and up-regulation of ICAM-1 expression. Continuous ICAM-1 expression might be related to stenosis of the eustachian tube.
Wang
Sheng-zi
SZ
Department of Radiotherapy and Oncology Eye, Ear, Nose and Throat Hospital of Fudan University, Shanghai, P.R. China. shengziwang@fudan.edu.cn
Chen
Zhong-chun
ZC
McNamar
Justin P
JP
Wang
Shu-yi
SY
Cheng
Qing-fang
QF
D004999:Amifostine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D004432:Ear, Middle / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D006168:Guinea Pigs; D018799:Intercellular Adhesion Molecule-1 / Q000187:drug effects* / Q000378:metabolism*; D009092:Mucous Membrane / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010033:Otitis Media / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D011829:Radiation Dosage; D011832:Radiation Injuries / Q000150:complications* / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000008:administration & dosage / Q000494:pharmacology*
D011837:Radiation-Protective Agents; D018799:Intercellular Adhesion Molecule-1; D004999:Amifostine