Radioprotective effects of DMA, a bisbenzimidazole against ionizing radiation in Balb/c mice

Radiotherapy is commonly being used in the treatment of cancer. For selective protection of normal tissues over tumor tissues, an effective and safe radioprotector is required. In our laboratory, Bisbenzimidazole (DMA), (5-(4-methylpiperazin-1-yl)-2-(2'(3,4-dimethoxyphenyl)-5' benzimidazolyl)benzimidazole) has been evaluated for its in vitro radioprotection in mammalian cell lines. In the present study, we explored DMA for its in vivo antioxidant potential and radioprotective efficacy against whole body exposure in Balb/c mice to ionizing radiation. To evaluate the radioprotective efficacy, dose reduction factor (DRF) and endogenous spleen colony forming assay were performed. Optimum dose of DMA was selected as 300 mg/kg body weight which showed maximum radioprotection. Whole body irradiation in mice 2 h after pretreatment with DMA orally, at a dose rate of 1.836 Gy/min reduced the radiation induced mortality and increased the survival. DRF was calculated by using the graded radiation dose (5, 6, 8, 9 and 10 Gy). DMA elevated radiation LD50/30 from 5.21 to 7.06 Gy, indicating the DRF of 1.35. DMA pretreatment also maintained the spleen index (spleen weight/body weight x 100) and stimulates the endogenous spleen colony forming units (CFU). Radiation induced fall in endogenous antioxidant enzymes in liver was prevented by DMA pretreatment and significant elevation of the endogenous antioxidant enzymes (GR, GST and SOD) and Glutathione in mice at 24 h post irradiation was observed. DMA also protected the mice against radiation damage by significantly reducing the lipid peroxidation. In the above study, we have proved the in vivo radioprotective potential of DMA against ionizing radiation. (author)