Immunomodulatory and cytoprotective role of RP-1 in gamma-irradiated mice.
RP-1 has been reported to provide protection against lethal gamma-irradiation in mice. The present study was undertaken to understand its mechanism of action, especially with respect to modulation of radiation-induced changes in immune cell function, plasma antioxidant potential, cell cycle perturbations, apoptosis in mouse bone marrow cells, and micronuclei frequency in mice reticulocytes. 2 Gy reduced mitogenic response of splenic lymphocytes significantly at 48 h. Pre-irradiation RP-1 treatment significantly countered the radiation-induced loss of splenocyte proliferation. RP-1 treatment, with or without radiation, suppressed macrophage activation as compared to control. Irradiation decreased plasma antioxidant status significantly (p < 0.05) at 1 and 2 h (4.8 +/- 0.224 and 4.9 +/- 0.057 mM Fe2+) as compared to control (6.29 +/- 0.733 mM Fe2+) that was countered by RP-1 pre-treatment significantly (p < 0.05). RP-1 and irradiation individually caused G2 delay in bone marrow cells. RP-1 pre-treatment augmented radiation-induced G2 delay and elicited significant (p < 0.05) recovery in S-phase fraction at 48 h in comparison to irradiated group. Radiation-induced apoptosis (3%) was significantly higher than the control. RP-1 pre-treatment further enhanced apoptosis frequency (7.2%) in bone marrow cells. RP-1 pre-treatment significantly (p < 0.05) reduced (1.23%) the radiation-induced MN frequency (2.9%) observed at 48 h post-irradiation interval. Since the radioprotective manifestation of RP-1 is mediated through multiple mechanisms, needs further investigation.
Goel
H C
HC
Department of Radiation Biology, Institute of Nuclear Medicine and Allied Sciences, Brig. SK Mazumdar Marg, Timarpur, Delhi, India. radbiol@nda.vsnl.in
Agrawala
P K
PK
Pathania
V
V
Malhotra
N
N
D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects; D002455:Cell Division; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D004396:Coloring Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D016195:G2 Phase / Q000187:drug effects; D005720:Gamma Rays; D008264:Macrophages / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000378:metabolism; D008297:Male; D051379:Mice; D048629:Micronuclei, Chromosome-Defective / Q000378:metabolism; D015162:Micronucleus Tests; D010936:Plant Extracts / Q000494:pharmacology*; D011035:Podophyllum / Q000378:metabolism; D011833:Radiation Injuries, Experimental; D011837:Radiation-Protective Agents / Q000494:pharmacology; D016196:S Phase / Q000187:drug effects; D013154:Spleen / Q000166:cytology; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D013997:Time Factors
D000975:Antioxidants; D004396:Coloring Agents; D010936:Plant Extracts; D011837:Radiation-Protective Agents; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue