a National Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues , Wuhan , Hubei , China ;
b Department of Toxicology and Pharmacology, Faculty of Veterinary Medicine , Universidad Complutense de Madrid , Madrid , Spain ;
Drug Metab Rev. 2016 May;48(2):159-82. doi: 10.1080/03602532.2016.1189560. Epub 2016 Jun 10.
Quinoxaline 1,4-dioxide derivatives (QdNOs) have been widely used as growth promoters and antibacterial agents. Carbadox (CBX), olaquindox (OLA), quinocetone (QCT), cyadox (CYA) and mequindox (MEQ) are the classical members of QdNOs. Some members of QdNOs are known to cause a variety of toxic effects. To date, however, almost no review has addressed the toxicity and metabolism of QdNOs in relation to oxidative stress. This review focused on the research progress associated with oxidative stress as a plausible mechanism for QdNO-induced toxicity and metabolism. The present review documented that the studies were performed over the past 10 years to interpret the generation of reactive oxygen species (ROS) and oxidative stress as the results of QdNO treatment and have correlated them with various types of QdNO toxicity, suggesting that oxidative stress plays critical roles in their toxicities. The major metabolic pathways of QdNOs are N→O group reduction and hydroxylation. Xanthine oxidoreductase (XOR), aldehyde oxidase (SsAOX1), carbonyl reductase (CBR1) and cytochrome P450 (CYP) enzymes were involved in the QdNOs metabolism. Further understanding the role of oxidative stress in QdNOs-induced toxicity will throw new light onto the use of antioxidants and scavengers of ROS as well as onto the blind spots of metabolism and the metabolizing enzymes of QdNOs. The present review might contribute to revealing the QdNOs toxicity, protecting against oxidative damage and helping to improve the rational use of concurrent drugs, while developing novel QdNO compounds with more efficient potentials and less toxic effects.
喹喔啉 1,4-二氧化物衍生物（QdNOs）被广泛用作生长促进剂和抗菌剂。卡巴氧（CBX）、奥拉喹多（OLA）、喹乙醇（QCT）、喹肟酯（CYA）和马兜铃酸（MEQ）是 QdNOs 的典型成员。一些 QdNOs 成员已知会引起多种毒性作用。然而，迄今为止，几乎没有评论涉及 QdNOs 与氧化应激有关的毒性和代谢。本综述重点介绍了与氧化应激作为 QdNO 诱导毒性和代谢的可能机制相关的研究进展。本综述记录了过去 10 年开展的研究，以解释 QdNO 处理产生的活性氧（ROS）和氧化应激，并将其与各种类型的 QdNO 毒性相关联，表明氧化应激在其毒性中起着关键作用。QdNOs 的主要代谢途径是 N→O 基团还原和羟化。黄嘌呤氧化还原酶（XOR）、醛氧化酶（SsAOX1）、羰基还原酶（CBR1）和细胞色素 P450（CYP）酶参与了 QdNOs 的代谢。进一步了解氧化应激在 QdNOs 诱导的毒性中的作用，将为抗氧化剂和 ROS 清除剂的使用以及代谢和 QdNOs 代谢酶的盲点提供新的思路。本综述可能有助于揭示 QdNOs 的毒性，防止氧化损伤，并有助于提高同时使用药物的合理性，同时开发具有更高效率和更少毒性的新型 QdNO 化合物。
