Monks T J, Lau S S
Division of Pharmacology and Toxicology, College of Pharmacy, University of Texas, Austin 78712.
Crit Rev Toxicol. 1992;22(5-6):243-70. doi: 10.3109/10408449209146309.
Cytotoxicity associated with exposure to quinones has generally been attributed to either redox cycling, and the subsequent development of "oxidative stress," and/or to their interaction with cellular nucleophiles, such as protein and non-protein sulfhydryls. Glutathione (GSH) is the major non-protein sulfhydryl present in cells, and conjugation of potentially toxic electrophiles with GSH is usually associated with detoxication and excretion. However, this review discusses the biological (re)activity of quinone-thioethers. For example, quinone-thioethers are (1) capable of redox cycling (2) substrates for, and inhibitors of, a variety of enzymes (3) methemoglobinemic (4) potent nephrotoxicants (5) DNA reactive and (6) may contribute to quinone-mediated carcinogenicity and neurotoxicity. The ubiquitous nature of quinones, and the high intracellular concentrations of GSH, ensures that cells and tissues will be exposed to quinone-thioethers. The toxicological importance of quinone-thioethers in quinone-mediated toxicities therefore deserves further attention.
与醌类物质接触相关的细胞毒性通常归因于氧化还原循环以及随后产生的“氧化应激”，和/或归因于它们与细胞亲核试剂（如蛋白质和非蛋白质巯基）的相互作用。谷胱甘肽（GSH）是细胞中主要的非蛋白质巯基，潜在有毒亲电试剂与GSH的结合通常与解毒和排泄有关。然而，本综述讨论了醌硫醚的生物（再）活性。例如，醌硫醚（1）能够进行氧化还原循环，（2）是多种酶的底物和抑制剂，（3）具有高铁血红蛋白血症作用，（4）是强效肾毒物，（5）具有DNA反应活性，（6）可能导致醌介导的致癌性和神经毒性。醌类物质的普遍存在以及细胞内高浓度的GSH，确保细胞和组织会接触到醌硫醚。因此，醌硫醚在醌介导的毒性中的毒理学重要性值得进一步关注。
