Phase 0 of the Xenobiotic Response: Nuclear Receptors and Other Transcription Factors as a First Step in Protection from Xenobiotics.

William S Baldwin

doi:10.32527/2019/101447

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

Introduction

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.

Results

Conclusion