Hepato-renal toxicity of concurrent metronidazole and azithromycin administration in mice: biochemical, oxidative stress, and histopathological evidence

Abstract

Medical professionals in both human and animal healthcare frequently use antibiotic therapy concurrently, but researchers have not fully studied the potential adverse effects of combined antibiotic therapy. Therefore, the aim of this study was to investigate the effects of repeated administration of metronidazole and azithromycin on liver and kidney function in mice, using integrated biochemical and histopathological assessments. Forty adult male mice (Swiss Albino) were randomly assigned to four groups (10 animals each): a control and three treatment groups reeiving metronidazole (125 g/kg/day) and azithromycin (30 mg/kg/day), either separately or together. Drugs were administered orally for 14 consecutive days. The laboratory tests included serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), blood urea nitrogen, and creatinine levels. Lipid peroxidation (MDA) and glutathione (GSH) tests were conducted on liver and kidney tissue samples, along with histopathological assessments using semi-quantitative scoring methods. The two monotherapy groups showed average increases in liver and kidney biomarkers that exceeded those of the control group. The combination group showed the highest increases in ALT, AST, urea, and creatinine levels. Oxidative profiling demonstrated that MDA levels rose and GSH levels decreased in all groups, but the combined-exposure group showed the greatest disruption. Histopathological analysis revealed that the liver and kidneys experienced different levels of damage, which were most pronounced in the combined-treatment group. The combination of metronidazole and azithromycin exposure during subacute conditions leads to increased hepato-renal toxicity, which results from oxidative stress and structural tissue damage. Therefore, cautious co-administration of this drug pair and further mechanistic research are warranted.