Non-cytochrome P450 enzyme aldehyde oxidase is involved in the oxidative metabolic pathway of diquat and its detoxification effect.

Autor: Mao Z; Department of Forensic Medicine, Nanjing Medical University, Nanjing, Jiangsu 211166, PR China; Institute of poisoning, Nanjing Medical University, Nanjing, Jiangsu 211166, PR China. Electronic address: maozhengsheng@njmu.edu.cn., Yu Y; Department of Forensic Medicine, Nanjing Medical University, Nanjing, Jiangsu 211166, PR China; Institute of poisoning, Nanjing Medical University, Nanjing, Jiangsu 211166, PR China., Ba G; Institute of poisoning, Nanjing Medical University, Nanjing, Jiangsu 211166, PR China; Department of Emergency, Jiangsu Province Hospital, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China., Zhao H; Department of Emergency Medicine, Huaian First People's Hospital, Huaian, PR China., Shi Q; Institute of poisoning, Nanjing Medical University, Nanjing, Jiangsu 211166, PR China; Department of Emergency, Jiangsu Province Hospital, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China., Cao Y; Department of Forensic Medicine, Nanjing Medical University, Nanjing, Jiangsu 211166, PR China., Xie W; Department of Forensic Medicine, Nanjing Medical University, Nanjing, Jiangsu 211166, PR China; Institute of poisoning, Nanjing Medical University, Nanjing, Jiangsu 211166, PR China., Zhang J; Institute of poisoning, Nanjing Medical University, Nanjing, Jiangsu 211166, PR China; Department of Emergency, Jiangsu Province Hospital, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China; Key Laboratory of Modern Toxicology of Ministry of Education, Nanjing Medical University, Nanjing, Jiangsu 211166, PR China., Sun H; Institute of poisoning, Nanjing Medical University, Nanjing, Jiangsu 211166, PR China; Department of Emergency Medicine, Nanjing Drum Tower Hospital, Nanjing, PR China; Key Laboratory of Modern Toxicology of Ministry of Education, Nanjing Medical University, Nanjing, Jiangsu 211166, PR China. Electronic address: haosun@njmu.edu.cn., Chen F; Department of Forensic Medicine, Nanjing Medical University, Nanjing, Jiangsu 211166, PR China; Institute of poisoning, Nanjing Medical University, Nanjing, Jiangsu 211166, PR China; Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University, Nanjing, Jiangsu 211166, PR China. Electronic address: fchen@njmu.edu.cn.
Jazyk: angličtina
Zdroj: Pesticide biochemistry and physiology [Pestic Biochem Physiol] 2024 Feb; Vol. 199, pp. 105805. Date of Electronic Publication: 2024 Jan 24.
DOI: 10.1016/j.pestbp.2024.105805
Abstrakt: Diquat (DQ) poisoning has garnered attention in recent years, primarily due to the rising incidence of cases worldwide, coupled with the absence of a viable antidote for its treatment. Despite the fact that diquat monopyridone (DQ-M) has been identified as a significant metabolite of DQ, the enzyme responsible for its formation remains unknown. In this study, we have identified aldehyde oxidase (AOX) as a vital enzyme involved in DQ oxidative metabolism. The metabolism of DQ to DQ-M was significantly inhibited by AOX inhibitors including raloxifene and hydralazine. The source of oxygen incorporated into DQ-M was proved to be from water through a H2 18 O incubation experiment which further corroborated DQ-M formation via AOX metabolism. The product of DQ-M in vitro generated by fresh rat tissues co-incubation was consistent with its AOX expression. The result of the molecular docking analysis of DQ and AOX protein showed that DQ is capable of binding to AOX. Furthermore, the cytotoxicity of DQ was significantly higher than DQ-M at the same concentration tested in six cell types. This work is the first to uncover the involvement of aldehyde oxidase, a non-cytochrome P450 enzyme, in the oxidative metabolic pathway of diquat, thus providing a potential target for the development of detoxification treatment.
Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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