Modeling regulatory and metabolic mechanismas for acetaminophen-induced hepatotoxicity

S. A. Guzikowski, M. G. Ierapetritou, C. M. Roth

Research output: Chapter in Book/Report/Conference proceedingConference contribution


Acetaminophen is a common over-the-counter analgesic and antipyretic drug with an excellent safety record when taken at therapeutic doses. However, acetaminophen causes a potentially irreversible and fatal hepatic centrilobular necrosis when taken in overdose. To investigate the mechanisms leading to acetaminophen-induced hepatotoxicity, regulatory and metabolic models are developed that elucidate the effects of acetaminophen metabolism as a means to reduce toxicity. The networks will be used to study different aspects of acetaminophen-induced hepatotoxicity including dose response, fasting, and cytochrome P450 activation. A kinetic model of acetaminophen metabolism illustrates the formation of toxic metabolites in a dose-dependent fashion and the requirement for conjugation species. Pathway analysis reveals the impact of acetaminophen on the overall hepatocyte metabolic network and identifies enzymes for perturbation and metabolic requirements. Rules based regulatory network may be used to show the connection between acetaminophen-induced hepatocyte signaling and induction of hepatotoxicity.

Original languageEnglish (US)
Title of host publicationProceedings of the IEEE 32nd Annual Northeast Bioengineering Conference, 2006
Number of pages2
StatePublished - 2006
EventIEEE 32nd Annual Northeast Bioengineering Conference, 2006 - Easton, PA, United States
Duration: Apr 1 2006Apr 2 2006

Publication series

NameBioengineering, Proceedings of the Northeast Conference
ISSN (Print)1071-121X


OtherIEEE 32nd Annual Northeast Bioengineering Conference, 2006
Country/TerritoryUnited States
CityEaston, PA

All Science Journal Classification (ASJC) codes

  • Bioengineering


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