Multiple effects of acetaminophen and p38 inhibitors: Towards pathway toxicology

The majority of drug-related toxicities are idiosyncratic, with little pathophysiological insight and mechanistic understanding. Pathway toxicology is an emerging field of toxicology in the post-genomic era that studies the molecular interactions between toxicants and biological pathways as a way to bridge this knowledge gap. Using two case studies - acetaminophen and p38 MAPK inhibitors - this review illustrates how a pathway-based perspective has advanced our understanding of compound and target-based toxicities. The advancement of pathway toxicology will be dependent on integrated applications of techniques from basic sciences and a fundamental understanding of the interdependence of multiple biological pathways in living organisms. (C) 2008 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.