Badawy Sara, Yang YaQin, Liu Yanan, Marawan Marawan A, Ares Irma, Martinez María-Aránzazu, Martínez-Larrañaga María-Rosa, Wang Xu, Anadón Arturo, Martínez Marta
National Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan, China.
Pathology Department of Animal Medicine, Faculty of Veterinary Medicine, Benha University, Benha, Egypt.
Crit Rev Toxicol. 2021 Oct;51(9):754-787. doi: 10.1080/10408444.2021.2024496.
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.
环丙沙星(CIP,用于人类)和恩诺沙星(ENR,用于兽医)是属于第二代氟喹诺酮类的合成抗感染药物。它们具有广泛的抗菌谱,通过对DNA复制所需的DNA回旋酶和拓扑异构酶IV的酶抑制作用,在极低浓度下就具有强大的杀菌效果。它们还具有高生物利用度,吸收迅速,药代动力学良好,组织穿透力强,包括脑脊液。这些特性使它们成为人类医学和兽医学中应用最广泛的抗生素。ENR仅用于动物医学,已被广泛用作治疗性兽用抗生素,导致其在可食用组织和水生环境中残留,以及产生耐药性和毒性。评估CIP和ENR产生的抗菌耐药性对人类的风险很重要且备受关注。此外,在极少数情况下,由于过量用药和/或长期给药,可能会出现CIP和ENR毒性。除了与代谢相关的毒性外,这些氟喹诺酮类抗菌药物的毒性主要与活性氧(ROS)的产生和氧化应激(OS)有关。因此,CIP在孕妇、哺乳期妇女、儿童和老年人中受到限制,同样,ENR在兽医领域也受到限制。这篇综述手稿旨在确定由ROS和OS诱导的毒性,这是CIP和ENR常见的后遗症。此外,还报道了它们的代谢以及代谢酶的作用。