Figure 1519

A-D, Similarities and differences between oxidant-induced and halocarbon-cysteine conjugate-induced renal proximal tubular lipid peroxidation and cell death. The model oxidant t-butylhy-droperoxide (TBHP) and the halocarbon-cysteine conjugate dichlorovinyl-L-cysteine (DCVC) caused extensive lipid peroxidation after 1 hour of exposure and cell death (lactate dehydrogenase (LDH) release) over 6-hours' exposure. The iron chelator deferoxamine (DEF) and the antioxidant N,N'-diphenyl-1, 4-phenylenediamine (DPPD) completely blocked both the lipid peroxidation and cell death caused by TBHP. In contrast, while DEF and DPPD completely blocked the lipid peroxidation caused by DCVC, cell death was only delayed. These results suggest that the iron-mediated oxidative stress caused by TBHP is responsible for the observed toxicity, whereas the iron-mediated oxidative stress caused by DCVC accelerates cell death. One reason that cells die in the absence of iron-mediated oxidative stress is that DCVC causes marked mitochondrial dysfunction. (Data from Groves et al. [8], and Schellmann [9].)

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