Abstract
This mini-review examines the crucial importance of transcription factors as a first line of defense in the detoxication of xenobiotics. Key transcription factors that recognize xenobiotics or xenobiotic-induced stress such as reactive oxygen species (ROS), include AhR, PXR, CAR, MTF, Nrf2, NF-κB, and AP-1. These transcription factors constitute a significant portion of the pathways induced by toxicants as they regulate phase I-III detoxication enzymes and transporters as well as other protective proteins such as heat shock proteins, chaperones, and anti-oxidants. Because they are often the first line of defense and induce phase I-III metabolism, could these transcription factors be considered the phase 0 of xenobiotic response?
Highlights
The term phase I and phase II detoxication have been a part of the lexicon of the toxicology vocabulary since first coined by R.T
Phase I refers to the early oxidative metabolism of the xenobiotic, and phase II typically refers to conjugation but potentially to a second oxidative reaction such as deepoxidation by epoxide hydrolase [3]
Many of the proteins induced by aryl hydrocarbon receptor (AhR) activation are detoxication enzymes and include CYP1A, CYP1B, NADPH:quinone oxidoreductase 1, and UDPglucuronosyltransferase 1 [32,33,34] of which several are necessary for the metabolism of the xenobiotic and protection from its adverse effects
Summary
The term phase I and phase II detoxication have been a part of the lexicon of the toxicology vocabulary since first coined by R.T. Many of the proteins induced by AhR activation are detoxication enzymes and include CYP1A, CYP1B, NADPH:quinone oxidoreductase 1, and UDPglucuronosyltransferase 1 [32,33,34] of which several are necessary for the metabolism of the xenobiotic and protection from its adverse effects.
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