Cytotoxicity of Some Nitroimidazole Derivatives - Comparative Studies on Human and Rat Hepatoma Cell Lines
Abstract The cytototoxic potential of metronidazole, tinidazole, ronidazole, and ornidazole, using human and rat hepatoma cell lines (HepG2 and FaO) in culture was assessed. The cells were treated with drugs for 24, 48 and 72 h at 37 °C in 5% CO2 at concentrations of 0.1 to 200 μg/mL. Following the treatment period, the cells were assayed by four independent assays: MTT reduction, neutral red uptake (NRU), total protein content (TPC), and LDH leakage. The results suggest that nitroimidazoles are of low cytotoxic potential (EC50 >200μg/mL). The exception was ronidazole, which demonstrated a distinct endpoint sensitivity related to the species. EC50 (μg/mL) in human cells were: in MTT assay - 196±5.5 and 122±9.3 at 24 and 48 h, respectively, and in NRU assay - 150±1.25 at 72 h. Based on minimal toxic concentrations (EC20) for ronidazole, determined by all methods used in HepG2 cells, it could be concluded that their sensitivity was as follows: MTT>NRU>LDH>TPC.
