Propagation of Pericentral Necrosis During Acetaminophen-Induced Liver Injury: Evidence for Early Interhepatocyte Communication and Information Exchange.

ABSTRACT: Acetaminophen (APAP)-induced liver injury is clinically significant, and APAP overdose in mice often serves as a model for drug-induced liver injury in humans. By specifying that APAP metabolism, reactive metabolite formation, glutathione depletion, and mitigation of mitochondrial damage within individual hepatocytes are functions of intralobular location, an earlier virtual model mechanism provided the first concrete multiattribute explanation for how and why early necrosis occurs close to the central vein (CV). However, two characteristic features could not be simulated consistently: necrosis occurring first adjacent to the CV, and subsequent necrosis occurring primarily adjacent to hepatocytes that have already initiated necrosis. We sought parsimonious model mechanism enhancements that

SUBMITTER: Kennedy RC 

PROVIDER: S-EPMC6484890 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature