Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Canada; Institute of Food and Radiation Biology, Bangladesh Atomic Energy Commission, Bangladesh.
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Canada.
Chem Biol Interact. 2021 Aug 25;345:109574. doi: 10.1016/j.cbi.2021.109574. Epub 2021 Jul 3.
Quinone Oxidoreductase 1 (NQO1) is an antioxidant enzyme that catalyzes the two-electron reduction of several different classes of quinone-like compounds (quinones, quinone imines, nitroaromatics, and azo dyes). One-electron reduction of quinone or quinone-like metabolites is considered to generate semiquinones to initiate redox cycling that is responsible for the generation of reactive oxygen species and oxidative stress and may contribute to the initiation of adverse drug reactions and adverse health effects. On the other hand, the two-electron reduction of quinoid compounds appears important for drug activation (bioreductive activation) via chemical rearrangement or autoxidation. Two-electron reduction decreases quinone levels and opportunities for the generation of reactive species that can deplete intracellular thiol pools. Also, studies have shown that induction or depletion (knockout) of NQO1 were associated with decreased or increased susceptibilities to oxidative stress, respectively. Moreover, another member of the quinone reductase family, NRH: Quinone Oxidoreductase 2 (NQO2), has a significant functional and structural similarity with NQO1. The activity of both antioxidant enzymes, NQO1 and NQO2, becomes critically important when other detoxification pathways are exhausted. Therefore, this article summarizes the interactions of NQO1 and NQO2 with different pharmacological agents, endogenous biochemicals, and environmental contaminants that would be useful in the development of therapeutic approaches to reduce the adverse drug reactions as well as protection against quinone-induced oxidative damage. Also, future directions and areas of further study for NQO1 and NQO2 are discussed.
醌氧化还原酶 1（NQO1）是一种抗氧化酶，可催化多种不同类别的醌样化合物（醌、醌亚胺、硝基芳烃和偶氮染料）的两电子还原。醌或醌样代谢物的单电子还原被认为会生成半醌，引发氧化还原循环，这是产生活性氧物种和氧化应激的原因，并可能导致药物不良反应和健康不良影响的发生。另一方面，醌类化合物的两电子还原对于通过化学重排或自动氧化进行药物激活（生物还原激活）似乎很重要。两电子还原降低了醌的水平和生成活性物质的机会，这些活性物质可以耗尽细胞内的巯基池。此外，研究表明，NQO1 的诱导或耗尽（敲除）分别与氧化应激的敏感性降低或增加相关。此外，醌还原酶家族的另一个成员，NRH：醌氧化还原酶 2（NQO2）与 NQO1 具有显著的功能和结构相似性。当其他解毒途径耗尽时，这两种抗氧化酶，NQO1 和 NQO2 的活性变得至关重要。因此，本文总结了 NQO1 和 NQO2 与不同药理制剂、内源性生化物质和环境污染物的相互作用，这对于开发治疗方法以减少药物不良反应以及防止醌诱导的氧化损伤将是有用的。此外，还讨论了 NQO1 和 NQO2 的未来方向和进一步研究领域。
