CYP2E1 Sensitizes the Liver to LPS- and TNF α-Induced Toxicity via Elevated Oxidative and Nitrosative Stress and Activation of ASK-1 and JNK Mitogen-Activated Kinases
Treatment with TNFα plus pyrazole causes mitochondrial injury. TNFα plus pyrazole causes mitochondrial injury as reflected by (a) increased mitochondrial swelling (decreased absorbance at 540 nm) or (b) decreased mitochondrial membrane potential as assayed by succinate-dependent decline in rhodamine 123 fluorescence. The decline in fluorescence after addition of succinate is reflective of the mitochondrial membrane potential. Note: this decline is very small in the mitochondria isolated from TNFα plus pyrazole-treated mice. In (a) the increased swelling produced by TNFα plus pyrazole is prevented by cyclosporine A (CsA), an inhibitor of the mitochondrial permeability transition.
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