Use of short term genotoxicological tests to study cytotoxic, genotoxic and cell death mechanism of metronidazole

Abstract

Metronidazole (MTZ) is a wonderful drug, which is used clinically to treat a wide range of bacterial and protozoal infections. This study aimed to achieve a precise characterization of the cytotoxic and genotoxic activities of MTZ in cultured human lymphocytes at therapeutic concentrations and to evaluate the possible cell death mechanism associated with it. A significant decrease in Mitotic Index (P < 0.001) as well as an increase in Sister Chromatid Exchange (P < 0.001) and Chromosomal Aberrations (P < 0.001) frequencies with no modifications in Replication Index was observed. DNA extracts of MTZ treated cells resulted in nucleosomal DNA ladder pattern after 48 h of cell treatment and this pattern correlated with a decrease in cellular viability (P < 0.001), morphological evidence of apoptosis and increase in the percentage of nuclei with hypodiploid DNA content (P < 0.001). We concluded that MTZ is genotoxic, cytotoxic and is able to modulate cell death through apoptotic mechanisms in the experimental design employed.