Perspective of the Induction of Liver Microsomal Cytochrome P450s by Chemical Compounds

The concept of hepatic induction of drug-metabolizing cytochrome P450s (P450s) by xenobiotics, including therapeutic drugs, was proposed in the early 1960s. A polycyclic aromatic hydrocarbon and phenobarbital have been the two major inducers used to investigate this induction mechanism. Currently, the mechanisms mediated by aryl hydrocarbon receptor and constitutive androstane receptor are well-established. In addition to mammals, insects and fungi also express P450s and induce them following exposure to insecticides. These induc-tions may have environmental consequences. Finding the molec-ular mechanism regulating these inductions will be of major interest in the future. SIGNIFICANCE STATEMENT This paper summarizes present and future of investigations into induction of drug-metabolizing enzymes.