Toxicity induced by ciprofloxacin and enrofloxacin: oxidative stress and metabolism

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.