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

Figure 1

Effect of pyrazole or LPS or LPS plus pyrazole on serum ALT (a) or AST (b) or liver histopathology (c). In (c), panels refer to (A) saline; (B) pyrazole-treated; (C) LPS-treated; (D) LPS plus pyrazole treated. Arrows show necrotic foci with inflammatory cell infiltration. Note: combined treatment with pyrazole plus TNFα produces liver injury. The CYP2E1 inhibitor, chlormethiazole (CMZ), protects against LPS plus pyrazole toxicity in mice. (d) ALT/AST levels. Sal: Saline-treated; P + L: pyrazole plus LPS treated: C + P + L, CMZ plus pyrazole plus LPS treated. (e) histopathology (top panels); 3-nitrotyrosine protein adducts (middle panels); 4-hydroxynonenal adducts (bottom panels). In all panels, panel (a) is the saline treated; panel (b) is the LPS plus pyrazole treated; panel (c) refers to the CMZ plus LPS plus pyrazole treated.