Whole body protection against lethal ionizing radiation in mice by REC-2001: a semi-purified fraction of Podophyllum hexandrum.
The current study has concentrated on assessment of the radioprotective potential of REC-2001, a semi-purified fraction of rhizomes of Podophyllum hexandrum, in Swiss albino Strain 'A' mice exposed to 10 Gy whole-body gamma radiation. Animals were treated with 10 and 15 mg/kg b wt (i.p.) of REC-2001 1h prior to exposure to a lethal dose of gamma-radiation (10 Gy) and observed upto 30 days. For analysis of maximum tolerable dose (MTD), LD(50) and acute toxic dose, different concentrations of the extract were administered to animals and their mortality and morbidity status was observed upto 72 h and one week, respectively. Dose reduction factor (DRF) was determined by exposing REC-2001 pre-treated mice to supra-lethal doses of gamma-radiation. Endogenous spleen colony forming units (CFU), DNA strand breaks in thymocytes (alkaline halo assay) and lipid degradation was studied to understand the mechanism of radioprotection. A single dose of REC-2001 (10 and 15 mg/kg b wt i.p.) exhibited >90% survival in the pre-treated irradiated group versus no survival in radiation control group. Single doses of upto 75 mg/kg b wt (i.p.) did not cause any mortality (MTD) in mice. REC-2001, a dose of 90 mg/kg b wt, resulted in 50% mortality (LD(50)), while the LD(100) was 115 mg/kg b wt REC-2001 exhibited a DRF of 1.62. CFU counts in the REC-2001 treated group were found significantly high (5.33/spleen) as compared to controls. Exposure of thymocytes to 10 Gy radiation resulted in increased halo diameter (45+/-3 microm) in comparison to untreated controls (8+/-1 microm). REC-2001 administration (500 microg/ml) decreased the halo diameter to 15+/-2 microm. Radiation-induced lipid degradation was also inhibited by REC-2001. The present study has revealed that REC-2001 is a promising radioprotective fraction that can be effectively used against lethal doses of gamma-radiation after further investigations in higher animal models.
Lata
M
M
Department of Radiation Biology, Institute of Nuclear Medicine and Allied Sciences, Delhi, India. drmanjugupta2003@yahoo.com
Prasad
J
J
Singh
S
S
Kumar
R
R
Singh
L
L
Chaudhary
P
P
Arora
R
R
Chawla
R
R
Tyagi
S
S
Soni
N L
NL
Sagar
R K
RK
Devi
M
M
Sharma
R K
RK
Puri
S C
SC
Tripathi
R P
RP
D000818:Animals; D028141:Berberidaceae; D001835:Body Weight; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use* / Q000633:toxicity; D005720:Gamma Rays; D053208:Kaplan-Meier Estimate; D019787:Linoleic Acid / Q000378:metabolism; D020714:Maximum Tolerated Dose; D051379:Mice; D008517:Phytotherapy; D011833:Radiation Injuries, Experimental / Q000188:drug therapy*; D011837:Radiation-Protective Agents / Q000627:therapeutic use*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013154:Spleen / Q000528:radiation effects; D014916:Whole-Body Irradiation / Q000401:mortality
D004365:Drugs, Chinese Herbal; D011837:Radiation-Protective Agents; D017382:Reactive Oxygen Species; C509544:Sinopodophyllum hexandrum extract; D019787:Linoleic Acid