Comparative Study on Synergistic Toxicity of Enrofloxacin Combined with Three Antibiotics on Proliferation of THLE-2 Cell

Little attention has been paid to the problem of the combined toxicity of accumulated antibiotics on humans from food and clinical treatments. Therefore, we used human hepatocytes to study the joint toxicity of four common antibiotics. The cytotoxicity of enrofloxacin (ENR), combined with ciprofloxacin (CFX), florfenicol (FFC), or sulfadimidine (SMD) on THLE-2 cells was determined by CCK-8 assays; then their joint toxicity was evaluated using CalcuSyn 2.0. Dose-effect curves and median-effect plots established on large amounts of data and CI values were calculated to judge the nature of the combination's interaction. ED50, ED75, and ED90 were predicted to elucidate the changing trend of the concentration on the toxicity of each drug pair. The ENR-CFX and ENR-FFC pairs exhibited synergistic toxicity only at special concentration rates, while ENR and SMD synergistically induced cytotoxicity at almost all the concentration rates studied. The mixed ratio was a significant factor for synergistic toxicity and should be evaluated in all combined effect studies. These results suggested that the combined toxicity of these four drugs should be taken into account in their risk assessment.

Automated summary

The study highlights the combined toxicity of four commonly used antibiotics on human hepatocytes. Synergistic toxicity was observed in certain combinations at specific concentrations, while others exhibited synergistic toxicity at almost all concentrations. The study emphasizes the significance of evaluating the mixing ratio in assessing the combined toxicity of antibiotics.