Metronidazole induces genotoxicity, hepato- and nephrotoxicity by triggering DNA fragmentation in Swiss albino mice...

In this study, toxic effects of metronidazole (Mtz) on albino mice, a non-target organism, were investigated using organ weight, genotoxicity assays, serum markers, liver and kidney histopathology. Mice were administered three different doses of Mtz (125-500 mg/kg, 250 mg/kg and 500 mg/kg) by oral gavage. The mice in each group were sacrificed at the end of the 14th day, blood and tissue samples were collected. Liver weight increased with Mtz treatment, the highest organ weight was 2.29 ± 0.22 g in the group treated with 500 mg/kg Mtz and increased by 57.9% compared to the control group. Similary, in the 500 mg/kg Mtz treated group, kidney organ weight was 0.59 ± 0.36 g and 37.3% increase was found compared to the control group. Mtz exposure caused statistically significant increases in the micronucleus (MN) frequency and chromosomal abnormalities (CAs), as well as a decrease in cell proliferation. Compared to the control group, mitotic index (MI) decreased by 6.8% in the 125 mg/kg b.w Mtz group, 16.5% in the 250 mg/kg Mtz group and 25.6% in the 500 mg/kg Mtz group. Comet assay revealed that Mtz exposure caused significant DNA fragmentation at all three treatment doses. Compared to the control group, the percentage of head DNA decreased by approximately 32% in the 500 mg/kg b.w Mtz treated group, while the percentage of tail DNA increased by 727%. MI, MN, CAs and Comet test results support each other and confirm the genotoxic effect of Mtz. Changes in serum marker enzymes indicate liver and kidney damage, which is also supported by histopathological examinations. Blood urea nitrogen levels increased by 16.7% and 25.8% in the 250 mg/kg and 500 mg/kg Mtz groups, respectively. The increase in creatinine levels ranged from 13 to 19.2%. In the 500 mg/kg Mtz-treated group, alanine aminotransferase and aspartate aminotransferase levels were also increased and these increases were 41% and 21.3%, respectively, compared to control. These abnormalities in liver and kidney markers were confirmed by histopathological examinations. Inflammation, glomerular hypertrophy, hyaline casts, crystal deposition, necrosis and tubular dilatation were found in the kidney. In the liver, inflammation, fibrosis, congestion, giant cells, apoptosis, necrosis, binuclear cells and hepatocyte hypertrophy were found. In conclusion, Mtz, which is used in the treatment of bacterial infections, may be toxic to albino mice, which are classified as mammals, such as humans. Consequently, a re-evaluation of the doses and administration times of Mtz, a pharmaceutical agent employed in the treatment of various infections, should be a priority for human health.