Toxicity induced by ciprofloxacin and enrofloxacin: oxidative stress and metabolism

Abstract

Ciprofloxacin (CIP) (human use) and enrofloxacin (ENR) (veterinary use) are synthetic anti-infectious medications that belong to the second generation of fluoroquinolones. They have a wide antimicrobial spectrum and strong bactericidal effects at very low concentrations via enzymatic inhibition of DNA gyrase and topoisomerase IV, which are required for DNA replication. They also have high bioavailability, rapid absorption with favorable pharmacokinetics and excellent tissue penetration, including cerebral spinal fluid. These features have made them the most applied antibiotics in both human and veterinary medicine. ENR is marketed exclusively for animal medicine and has been widely used as a therapeutic veterinary antibiotic, resulting in its residue in edible tissues and aquatic environments, as well as the development of resistance and toxicity. Estimation of the risks to humans due to antimicrobial resistance produced by CIP and ENR is important and of great interest. Moreover, in rare cases due to their overdose and/or prolonged administration, the development of CIP and ENR toxicity may occur. The toxicity of these fluoroquinolones antimicrobials is mainly related to reactive oxygen species (ROS) and oxidative stress (OS) generation, besides metabolism-related toxicity. Therefore, CIP is restricted in pregnant and lactating women, pediatrics and elderly similarly ENR do in the veterinary field. This review manuscript aims to identify the toxicity induced by ROS and OS as a common sequel of CIP and ENR. Furthermore, their metabolism and the role of metabolizing enzymes were reported.

Keywords:

• Ciprofloxacin
• enrofloxacin
• toxicity
• reactive oxygen species
• oxidative stress
• metabolism

Acknowledgments

The authors gratefully acknowledge the external reviewers selected by the Editor and anonymous to the authors whose comments were very valuable in revising and refining the manuscript. All authors gave final approval and agreed to be accountable for all aspects of work in ensuring that questions relating to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Declaration of interest

The manuscript was written as part of the authors’ normal employment. No potential conflict of interest was reported by the authors. The affiliation of the authors is as shown on the cover page. The views presented in this manuscript are those of the authors based on many years of research in the respective areas of investigation reported in this paper. Each author participated in the review process and preparation of this paper as an independent professional. No individuals other than the cited authors below were involved in the interpretation and conclusions of the manuscript prior to its submission to the journal. This work was supported by the National Key Research and Development Program of China (2018YFC1603005), the Fundamental Research Funds for the Central Universities (2662020DKPY020), and by the Project Ref. PID2020-115979RR-C33 from Ministerio de Ciencia e Innovación, Spain.