The acute-phase protein alpha2-macroglobulin plays an important role in radioprotection in the rat.
The importance of alpha2-macroglobulin (alpha2M) in natural radioprotection was studied by examining its radioprotective effectiveness in rat models of exogenously and endogenously, preexposure-increased alpha2M. Radioprotective efficacy was ascertained by the postirradiation survival rate, the restoration of body weight, and the leukocyte count, which were monitored during a 4-week follow-up period. The results were compared with the effects of a pretreatment with the synthetic radioprotective agent amifostine (Ami), which provides 100% protection in rats whole-body-irradiated by x-rays given in a dose of 6.7 Gy (LD50/30). Raising the plasma concentration of alpha2M 15-fold in male rats by a single intraperitoneal injection of purified protein provided 100% survival of irradiated animals. Female rats on the 19th day of pregnancy with endogenously elevated levels of alpha2M displayed improved survival (80%) compared with untreated rats (50% survival). After alpha2M administration, the pregnant, irradiated rats exhibited 100% survival. In both males and pregnant females, alpha2M administration promoted body weight and leukocyte postirradiation recovery as in Ami-pretreated rats. These findings, together with our observation that Ami administration induced a 45-fold increase in alpha2M in the circulation, led us to conclude that alpha2M has an essential role in both natural and amifostine-mediated radioprotection in the rat.
Institute for Biological Research Sinisa Stanković, Bulevar Despota Stefana 142, 11060 Belgrade, Serbia. mista@ibiss.bg.ac.yu
Mirjana
M
Mihailović
Silva
S
Dobrić
Goran
G
Poznanović
Miodrag
M
Petrović
Aleksandra
A
Uskoković
Jelena
J
Arambasić
Bogojević
B
Bogojević
D004999:Amifostine / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects / Q000528:radiation effects; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D007958:Leukocyte Count; D008297:Male; D011247:Pregnancy; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015996:Survival Rate; D014965:X-Rays / Q000009:adverse effects; D000511:alpha-Macroglobulins / Q000494:pharmacology*
D011837:Radiation-Protective Agents; D000511:alpha-Macroglobulins; D004999:Amifostine