Quinone-mediated cell damage

DNA breaks in human MCF-7 cells [65], Damaging effect of menadione was probably mediated by hydroxyl radicals as it was demonstrated by ESR spin-trapping method. The analogs of menadione 2-methylmethoxynaphthoquinone and 2-chloromethylnaphtho-quinone also stimulated DNA damage through the formation of superoxide and other free radicals [66]. Similar effects have been shown for hydroquinone, catechol, benzoquinone, and benzenetriol [67,68]. 

As hydroxyl or hydroxyl-like radicals are produced by the superoxide-driven Fenton reaction, superoxide overproduction must also occur in thalassemic cells. First, it has been shown by Grinberg et al. [382], who demonstrated that thalassemic erythrocytes produced the enhanced amount of superoxide in comparison with normal cells in the presence of prooxidant antimalarial drug primaquine. Later on, it has been found that the production of superoxide and free radical-mediated damage (measured through the MetHb/Hb ratio) was much higher in thalassemic erythrocytes even in the absence of prooxidants, although quinones (menadione, l,4-naphthoquinone-2-methyl-3-sulfonate) and primaquine further increased oxidative stress [383]. Overproduction of superoxide was also observed in thalassemic leukocytes [384]. 

In correlation with the nature of compounds that can induce ARE-driven transcription, many of the proteins whose expression is mediated by the ARE have an endogenous role in regulating cellular redox status and protecting the cell from oxidative damage. Enzymes such as GST, NQOl, and HO-1 function to detoxify harmful by-products of oxidative stress, including lipid and DNA base hydroperoxides (29,30), quinones (31), and heme-containing molecules (32). The induction of enzymes involved in GSH biosynthesis leads to an increase in cellular GSH levels that provides a buffer against oxidative insult (2). 

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