A new parameter for quantitatively characterizing antibiotic hormesis: QSAR construction and joint toxic action...

Area of Science:

• Environmental toxicology
• Pharmacology
• Bacterial resistance

Background:

• Antibiotics exhibit hormetic effects (low-dose stimulation, high-dose inhibition), challenging traditional toxicity assessments.
• Existing parameters inadequately quantify these complex biphasic dose-responses.
• Understanding antibiotic hormesis is crucial for accurate environmental risk evaluation.

Purpose of the Study:

• To develop a quantitative parameter, effective area in hormesis (A_H), to characterize antibiotic hormesis.
• To construct quantitative structure-activity relationship (QSAR) models for predicting A_H values.
• To establish a method for evaluating the joint toxic actions of antibiotic mixtures.

Main Methods:

• Quantified hormesis using effective area in hormesis (A_H) for single antibiotics (sulfonamides, sulfonamide potentiators, tetracyclines) and binary mixtures.
• Utilized E_bind and K_ow as structural descriptors to build QSAR models for A_H.
• Developed a novel method based on A_H to assess joint toxic actions of binary antibiotic mixtures.

Main Results:

• Successfully developed and applied the effective area in hormesis (A_H) parameter.
• Constructed reliable QSAR models for predicting A_H values of antibiotics and their mixtures.
• Identified synergistic joint toxic actions in most binary antibiotic mixtures, with sulfonamide potentiators or tetracyclines contributing more to hormesis.

Conclusions:

• The effective area in hormesis (A_H) provides a novel quantitative measure for antibiotic hormesis.
• QSAR models enable prediction of A_H values, facilitating risk assessment.
• This approach enhances the understanding of combined antibiotic effects, promoting better environmental risk evaluation.