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Multiple effects of acetaminophen and p38 inhibitors: towards pathway toxicology
Jinghai J Xu1, Bart S Hendriks, Jie Zhao
1Systems Biology, Pfizer Research Technology Center, 620 Memorial Drive, Cambridge, MA 02139, United States. jim.xu@pfizer.com
Abstract:
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.
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