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.
Xu
Jinghai J
JJ
Systems Biology, Pfizer Research Technology Center, 620 Memorial Drive, Cambridge, MA 02139, United States. jim.xu@pfizer.com
Hendriks
Bart S
BS
Zhao
Jie
J
de Graaf
David
D
D000082:Acetaminophen / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology* / Q000633:toxicity; D012867:Skin / Q000201:enzymology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*
D047428:Protein Kinase Inhibitors; D000082:Acetaminophen; D048051:p38 Mitogen-Activated Protein Kinases