Preclinical Evaluation of DMA, a Bisbenzimidazole as Radioprotector: Toxicity, Pharmacokinetics and Biodistribution Studies in Balb/c Mice

摘要: Radiotherapy, a therapeutic modality of cancer treatment, nonselectively damages normal tissues as well tumor tissues. The search is ongoing for agents that selectively reduce radiation-induced tissue injury without reducing tumoricidal effect, thereby increasing the ratio radiation therapy. Our laboratory established 5-(4-methylpiperazin-1-yl)-2-[2'-(3,4-dimethoxyphenyl)-5'benzimidazolyl] benzimidazole (DMA) noncytotoxic radioprotector in mammalian cells. DMA showed an excellent radioprotection mice at single nontoxic oral dose by dose-reduction factor 1.28. An oxygen radical absorbing capacity assay confirmed its free-radical quenching ability. Single bolus and 28-days repeated administration toxicity studies determined LD50 >2000 mg/kg body weight (bw) 225 bw, respectively, suggesting safe. Histopathology, biochemical parameters, relative organ analysis revealed insignificant changes DMA-treated animals. pharmacokinetic study intravenous doses C(max) = 1 hour, bioavailability 8.84%, elimination half-life 4 hours, enterohepatic recirculation. Biodistribution with Ehrlich ascites tumors (99m)Tc-DMA achieved highest concentration hour was retained up to hours lungs, liver, kidneys, spleen, low tumor, solicited property any protect cells over cancerous We observed single-dose treatment tumor-bearing 2 before 8 Gy total irradiation impressive rescue morbidity terms loss mortality change response.