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.
Juan Liu,Hou-Yi Zhao,Zi-Wen Liu,Peng-Yu Chen,Shao-Ping Tao,Lan Wu,Gui-Hua Li,Lu-Juan Cui,Qi Lin
Comprehensive Summary Hydrazine hydrate (DH) is a widely used chemical agent, but it is highly toxic. Thus, the development of low-cost and easy-to-prepare materials for the detection and adsorption of DH is very significant. Herein, a novel and easy-to-prepare supramolecular smart material based on bisquinoline-functionalized naphthalene diimide ( DQ8 ) has been designed and synthesized. In the DQ8 , the synergistic effect between quinoline and naphthalene diimide groups has been employed to improve the selectivity and sensitivity for binding of DH. The DQ8 -based crystalline porous material ( DQ8 -CPM) can simultaneously detect and adsorb DH and produce noticeable fluorescence color changes after adsorption of DH vapor. More significantly, the DQ8 -CPM shows nice recycling performance on DH detection and adsorption. Meanwhile, a smart gel based on DQ8 ( DQ8 -G) shows multi-channel response for DH through color, fluorescence, and state changes. The DQ8 shows high selectivity and sensitivity for DH. The detection limit of DQ8 for DH is 8.6 × 10 –7 mol/L. According to the investigation of the DH binding and response mechanism, the synergistic effect between quinoline and naphthalene diimide groups plays an important role in the DH response process. It's a simple and feasible way to develop materials for detection and adsorption of DH through synergistic effects.