Tissue-protective effects of fullerenol C60(OH)24 and amifostine in irradiated rats.
Polyhydroxylated fullerenes, named fullerenols (C(60)(OH)(n); n=12-26) are excellent antioxidants. Harmful effects of ionizing radiation on living organism are mainly mediated by free radical species and fullerenols attract an attention as a potential radioprotectors. Our preliminary investigations on mice and rats subjected to radiation injury show that fullerenol C(60)(OH)(24) provides high survival rate of irradiated small rodents. Radioprotective effect was comparable to that of the standard radioprotector amifostine. The aim of this study was to compare the efficacy of fullerenol C(60)(OH)(24) (10 and 100mg/kg i.p.) and amifostine (300 mg/kg i.p.) in protection of rats against harmful effects of ionizing radiation. The animals were whole-body irradiated by X-rays (8 MV). Both compounds were given 30 min before irradiation. In order to evaluate the general radioprotective efficacy of fullerenol and amifostine rats were irradiated with an absolutely lethal dose of X-rays (8 Gy) and their survival and body mass gain were monitored during the period of 30 days after irradiation. The aim of the second part of the study is to investigate the tissue-protective effects of tested compounds (100 mg/kg i.p. of fullerenol and 300 mg/kg i.p. of amifostine, 30 min before irradiation). It was carried out on rats irradiated with a sublethal dose of X-rays (7 Gy). Influence of ionizing radiation on hematopoesis as well as the radioprotective efficiency of the compounds given were evaluated by determining blood cell count during 28 days after irradiation. For this purpose the blood was taken from tail vein before irradiation and on the 3rd, 7th, 14th, 21st and 28th day after irradiation. In order to estimate the radioprotective effects of fullerenol and amifostine on other rat tissue, the animals were sacrificed on the 7th and 28th day after irradiation and their main organs (lung, heart, liver, kidney, small intestine and spleen) were taken for histopathological analysis. In the experiment in which the general radioprotective efficacy of fullerenol and amifostine was examined, fullerenol given in a dose of 100mg/kg produced better protection than given in a dose of 10mg/kg. This effect was comparable to that of amifostine. The results of hematological investigations showed that fullerenol better than amifostine prevented radiation-induced reduction in the white cell count (granulocytes and lymphocytes), particularly in the first 7 days after irradiation. Pathohistology examinations revealed better radioprotective effects of fullerenol compared to those of amifostine on the spleen, small intestine and lung, while amifostine had better radioprotective effects than fullerenol in protection of the heart, liver and kidney. These results confirm satisfactory radioprotective efficacy of fullerenol and encourage further investigations as a potential radioprotector.
Trajković
Sanja
S
Military Medical Academy, Belgrade, Serbia and Montenegro. sanja.trajkovic@uky.edu
Dobrić
Silva
S
Jaćević
Vesna
V
Dragojević-Simić
Viktorija
V
Milovanović
Zoran
Z
Dordević
Aleksandar
A
D004999:Amifostine / Q000494:pharmacology*; D000818:Animals; D001773:Blood Cells / Q000528:radiation effects; D037741:Fullerenes / Q000494:pharmacology*; D007421:Intestine, Small / Q000528:radiation effects; D008168:Lung / Q000528:radiation effects; D008297:Male; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013154:Spleen / Q000528:radiation effects; D014965:X-Rays / Q000009:adverse effects*
D037741:Fullerenes; D011837:Radiation-Protective Agents; C108127:fullerenol; D004999:Amifostine