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
TNFα-plus-pyrazole-induced hepatotoxicity and oxidative stress are decreased in iNOS knockout mice. B6-129 WT mice and B6-129 iNOS knockout mice (NOS2−/−) were treated with either saline or pyrazole alone or TNFα alone or pyrazole plus TNFα for 3 days followed by assays of (a) ALT/AST, (b) TBARS, and (c) GSH. Note: liver injury and oxidant stress were much lower in the NOS2−/− mice than the WT mice indicating a role for NO and NO metabolites in the TNFα-plus-pyrazole-induced liver injury and oxidative stress.
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