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The Xenobiotic Elimination System: An Overview (pp. 47-86) $100.00
Authors:  (Jane Alcorn, College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK, Canada)
Abstract:
The chapter presents an overview of the xenobiotic elimination system from the
perspective of an oral xenobiotic exposure. It notes the interrelationship of the three
elimination organs, liver, kidney, and intestine, and their respective roles in limiting
systemic exposures. The polarized epithelia of each elimination organ are highlighted as
these are the ‘workhorses’ of xenobiotic elimination and express the transporters and
enzymes that ultimately cause xenobiotic removal from the body. Emphasis is placed on
the four phases of xenobiotic elimination, phase 0 transporter-mediated xenobiotic uptake
into the polarized epithelia, phase I and phase II xenobiotic metabolism within the
polarized epithelia, and phase III transporter-mediated xenobiotic efflux from the
polarized epithelium. Hence, the chapter provides a general summary of the solute carrier
transporters of phase 0 elimination, the cytochrome P450 enzymes of phase I metabolism,
the conjugating enzymes of phase II metabolism, and the ATP binding cassette
transporters of phase III elimination. Finally, it offers an overview of the genetic,
environmental, and host factors influencing the activity of these individual elimination
mechanisms, as well as the transcriptional factors that regulate and coordinate their
expression. An extensive interplay between the various xenobiotic elimination
mechanisms requires that the xenobiotic is positioned within an integrated xenobiotic
elimination system to truly understand xenobiotic exposure outcomes. 


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The Xenobiotic Elimination System: An Overview (pp. 47-86)