Evaluation of the Hepato-Pancreatic Toxicities of Selected Antibiotics in Male Wistar Rats

Background and Purpose: The misuse and toxicity of antibiotics remain significant public health concerns, with implications extending beyond hepatotoxicity to include pancreatic injury. This study investigated the toxic effects of selected antibiotic drugs (amoxicillin, ciprofloxacin, erythromycin and metronidazole) on the liver and pancreas of male Wistar rats. Methods: Adult male Wistar rats were randomly assigned into five groups (n=5 per group). Group I served as the control and received normal saline. Groups II to V received ciprofloxacin (86 mg/kg), amoxicillin (129 mg/kg), erythromycin (86 mg/kg), and metronidazole (69 mg/kg), respectively. Administration was by the oral route for 21 or 42 days. Plasma insulin, nuclear factor kappa-beta (NFK-?), liver function enzymes (AST and ALT), lipid profile, and caspase-3 activity in liver and pancreas were evaluated. Histology and immunohistochemistry were performed on the liver and pancreas. Results: Erythromycin significantly elevated serum AST and ALT levels, indicating hepatocellular injury. LDL levels rose following a 21-day metronidazole exposure and a 42-day ciprofloxacin and amoxicillin administration, while HDL levels declined across all antibiotic groups, demonstrating a consistent dyslipidemic effect. Metronidazole altered insulin levels differently in 21 days and 42 days durations, suggesting duration-dependent metabolic modulation. NFK-? levels increased significantly in metronidazole and erythromycin groups, indicating a heightened inflammatory response. In the 21-day treatment, hepatic caspase-3 activity was significantly elevated in the amoxicillin and erythromycin groups, indicating enhanced hepatocyte apoptosis. Conversely, pancreatic caspase-3 levels were significantly reduced in these same groups, suggesting suppression of pancreatic apoptotic activity. In contrast, during the 42-day treatment, pancreatic caspase-3 levels were markedly increased in the ciprofloxacin and metronidazole groups. Immunohistochemistry revealed disrupted hepatic and pancreatic architecture across all treated groups. Conclusion: Ciprofloxacin, erythromycin, and metronidazole induced significant metabolic, inflammatory, and histopathological alterations in hepatic and pancreatic tissues. These findings underscore the need for cautious use and monitoring of these antibiotics to mitigate organ-specific toxicities.