The difference between the effects of both QIs on the cell viability ( Figure 2 ) and caspase 3 activation ( Figure 4 ) suggests that upon GSH depletion, the decrease in cell viability is not only apoptosis dependent but also most likely depends other cell death pathways, such as necrosis ( IC 50 values of QIs under GSH-depleted conditions were around 20 M ( Figure 2 ), which is higher than the plasma concentrations of AQ and DEAQ found in patients, normally in nanomolar to micromolar ranges ( in vivo may be lower, exposure continues for a prolonged period as the half-life of DEAQ is 10 to 12 days ( The relative contribution of GSTP1 to GSH-conjugation of both QIs was highest at GSH-depleted conditions, while in absolute quantities a higher GSTP1-dependent increase of GSH conjugate formation was seen without BSO pre-treatment ( Figure 5 )
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