CYP2E1 Sensitizes the Liver to LPS- and TNF <i>α</i>-Induced Toxicity via Elevated Oxidative and Nitrosative Stress and Activation of ASK-1 and JNK Mitogen-Activated Kinases

<table>Pyrazole potentiates TNF<i>α</i> hepatotoxicity and oxidative stress in mice. Mice were treated with either saline or pyrazole alone or TNF<i>α</i> alone or pyrazole plus TNF<i>α</i> followed by assays for (a) serum ALT/AST, (b) histopathology (arrows show necrotic zones), (c) lipid peroxidation as reflected by levels of TBARs in liver cell lysates and in isolated mitochondrial fractions. Note: combined treatment with TNF<i>α</i> plus pyrazole produces liver injury. (d) Serum ALT and AST levels in pyrazole plus TNF<i>α</i>-treated wild type (WT) and CYP2E1 knockout (KO) mice. (e) Histopathology in pyrazole plus TNF<i>α</i>-treated KO (panel A) and WT (panel B). Note: liver injury is decreased in CYP2E1 knockout mice compared to WT mice.</table>

International Journal of Hepatology

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Figure 2: CYP2E1 Sensitizes the Liver to LPS- and TNF <i>α</i>-Induced Toxicity via Elevated Oxidative and Nitrosative Stress and Activation of ASK-1 and JNK Mitogen-Activated Kinases 

Figure 2 | 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 