Whole body protection against lethal ionizing radiation in mice by REC-2001: A semi-purified fraction of Podophyllum hexandrum

Abstract 

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 10Gy whole-body gamma radiation. Animals were treated with 10 and 15mg/kgbwt (i.p.) of REC-2001 1h prior to exposure to a lethal dose of γ-radiation (10Gy) and observed upto 30 days. For analysis of maximum tolerable dose (MTD), LD₅₀ and acute toxic dose, different concentrations of the extract were administered to animals and their mortality and morbidity status was observed upto 72h and one week, respectively. Dose reduction factor (DRF) was determined by exposing REC-2001 pre-treated mice to supra-lethal doses of γ-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 15mg/kgbwt i.p.) exhibited >90% survival in the pre-treated irradiated group versus no survival in radiation control group. Single doses of upto 75mg/kgbwt (i.p.) did not cause any mortality (MTD) in mice. REC-2001, a dose of 90mg/kgbwt, resulted in 50% mortality (LD₅₀), while the LD₁₀₀ was 115mg/kgbwt 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 10Gy radiation resulted in increased halo diameter (45±3μm) in comparison to untreated controls (8±1μm). REC-2001 administration (500μg/ml) decreased the halo diameter to 15±2μm. 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 γ-radiation after further investigations in higher animal models.

Keywords: Podophyllum hexandrum, Radioprotection, Antioxidants, Lignans, DNA damage, Reactive oxygen species