The critical role of oxidative stress in the toxicity and metabolism of quinoxaline 1,4-di-N-oxides in vitro and in vivo.
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.
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 ;
Xu
X
Wang
b Department of Toxicology and Pharmacology, Faculty of Veterinary Medicine , Universidad Complutense de Madrid , Madrid , Spain ;
María-Aránzazu
MA
Martínez
c MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products , Huazhong Agricultural University , Wuhan , Hubei , China ;
Guyue
G
Cheng
d Hunan Engineering Research Center of Veterinary Drugs, College of Veterinary Medicine , Hunan Agricultural University , Changsha , Hunan , China ;
Zhaoying
Z
Liu
c MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products , Huazhong Agricultural University , Wuhan , Hubei , China ;
Lingli
L
Huang
c MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products , Huazhong Agricultural University , Wuhan , Hubei , China ;
Menghong
M
Dai
c MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products , Huazhong Agricultural University , Wuhan , Hubei , China ;
Dongmei
D
Chen
b Department of Toxicology and Pharmacology, Faculty of Veterinary Medicine , Universidad Complutense de Madrid , Madrid , Spain ;
María-Rosa
MR
Martínez-Larrañaga
b Department of Toxicology and Pharmacology, Faculty of Veterinary Medicine , Universidad Complutense de Madrid , Madrid , Spain ;
Arturo
A
Anadón
a National Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues , Wuhan , Hubei , China ;|c MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products , Huazhong Agricultural University , Wuhan , Hubei , China ;|e Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety , Wuhan , Hubei , China.
Zonghui
Z
Yuan
D000818:Animals; D006801:Humans; D018384:Oxidative Stress; D011810:Quinoxalines / Q000378:metabolism* / Q000493:pharmacokinetics / Q000633:toxicity*
D011810:Quinoxalines
Quinoxaline; antioxidants; carbadox; cyadox; mequindox; olaquindox; oxidative stress; quinocetone; reactive oxygen species