Metronidazole promotes oxidative stress and DNA fragmentation-mediated myocardial injury in albino mice.

The purpose of the present study was to investigate the cardiotoxic effects of Metronidazole (Mtz) in albino mice. The mice were divided into four experimental groups: Gp.I (control group): saline, Gp.II:125 mg/kg b.w Mtz, Gp.III:250 mg/kg b.w, Gp.IV:500 mg/kg b.w Mtz. Heart weight ratio, markers of cardiac injury, markers of oxidative stress, histopathological examinations, DNA fragmentation and spectral analysis were used to determine cardiotoxicity. Administration of 125-500 mg/kg Mtz caused an increase in heart weight and a decrease in body weight. Administration of 500 mg/kg Mtz increased heart weight by 35.5% and decreased body weight by 21.9% compared with control. Mtz-treated mice showed a significant increase in cardiac injury biomarkers and serious alterations in cardiac oxidative stress markers. Histopathological changes of cardiac tissues observed in mice treated with Mtz include myocardial hypertrophy, fibrosis, myocarditis, separation of the muscle fibers, congestion-narrowing in vessels, necrosis, myocardium-vacuolation, myocytolysis, myocyte degeneration, nuclear aggregation, cytoplasmic fragmentation and prevalent nuclei. Mtz treatment already resulted in a significant decrease in the percentage of head DNA and an increase in the percentage of tail DNA. The most striking tail formation among the Mtz-treated groups was observed in the group receiving 500 mg/kg Mtz. In the presence of Mtz, there was a hypochromic shift in the absorption spectrum of DNA, and the potential DNA-Mtz interaction was found to occur in the intercalation mode. These results show that Mtz used against anaerobic bacteria and protozoa in gastrointestinal infections can cause severe cardiotoxic findings in albino mice and cause fragmentation in DNA.