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Rosenberg & Hanna, 2000

Figure 2 2.1 Disruption of airway epithelial cells functions The pulmonary epithelium serves as the first line of defense against inhaled pathogens and harmful particles, acting as a physical barrier, and an integral part of the innate immune system (6163)

Ann Intern Med 91:528, 1979

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By the end of this post, medical toxicology fellows will recognize and understand: Similar APAP toxicity chain of events in mouse models and human beings Initial NAPQI-induced toxicity characterized by superoxide release from electron transport chain (ETC) complex III Activated JNK produces superoxide release from ETC complex I An amplified oxidative/nitrosative cycle maintains persistent JNK activation and peroxynitrite formation Peroxynitrites important role in producing hepatocellular necrosis Fomepizole demonstrates 2 mechanisms of action: inhibition of CYP2E1, and inhibition of JNK Fomepizoles inhibition of JNK prevents necrosis in mice and human liver cells long after NAPQI formation and GSH depletion It looks complicated, but it is easy to understand if we start at the beginning and build on each step