Genotoxic and cytotoxic effects of the novel immunosuppressive agent 3-[(1-methyl-4-nitro-~1H-imidazol-5-yl)thio]-4-methyl-1,2,4-triazole (MNITMT) on mouse bone marrow cells

摘要

3-[(1-methyl-4-nitro-~1H-imidazol-5-yl)thio]-4-methyl-1,2,4-triazole (MNITMT) is an immunosuppressive agent used to treat autoimmune disorders. The objectives of this study were to determine the genotoxic and cytotoxic effects of MNITMT on bone marrow cells of mice. Various concentrations of MNITMT were tested (2, 5, 10 and 20 mg ml~(-1)). Bone marrow cells were prepared for mitotic and mitodepressive indices and blood smears for micronuclei. Cell viability of cultured bone marrow cells was determined using an MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide)] assay and the proliferation index was calculated. Our results show that MNITMT significantly lowered the mitotic index (MI) at the highest two doses (10 and 20 mg ml ~(-1)) with 14.3 % and 14.9 % at 24 h, 19.2 % and 19.6 % at 48 h, 15.4 % and 19.8 % at 72 h, respectively as compared to control. The percentage of micronuclei (MN) increased with increasing the MNITMT doses 2, 5, 10 and 20 mg ml~(-1) (79, 125, 141 and 145% respectively). Administration of 2, 5 and 10 mg ml~(-1) of MNITMT did not cause any bone marrow toxicity, while approximately 50% reduction in the rate of proliferation was observed using the highest dose, 20 mg ml~(-1). These results suggest that high doses of MNITMT cause both genotoxic and cytotoxic effects.