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ARS Home » Southeast Area » Little Rock, Arkansas » Arkansas Children's Nutrition Center » Research » Publications at this Location » Publication #201081
Title: Developmental Effects on Xenobiotic Metabolism

Author
item RONIS, MARTIN - ACNC/UAMS
item CUNNY, HELEN - BEYER CROP SCIENCES

Submitted to: Book Chapter
Publication Type: Book / Chapter
Publication Acceptance Date: 1/15/2007
Publication Date: 8/18/2008
Citation: Ronis, M.J., Cunny, H. 2008. Developmental effects on xenobiotic metabolism. In: Smart, R.C., Hodgson, E., editors. Molecular and Biochemical Toxicology. 4th edition. Hoboken, NJ: Wiley and Sons, Inc. p. 257-272.

Interpretive Summary:

Technical Abstract: Many physiological factors influence the rate of disappearance of drugs and other foreign chemicals from the body and the relative importance of different pathways of drug activation or inactivation. It has become increasingly clear in recent years that in addition to the disposal of endogenous waste products such as bilirubin and breakdown of drugs and dietary and environmental chemicals, drug metabolizing enzymes originally evolved to regulate endogenous processes. These include steroid biosynthesis and degradation; fatty acid; and vitamin metabolism, which controls ligand availability to a large family of nuclear receptors and other transcription factors. Activation of these transcription factors, in turn, controls patterns of gene transcription important in development; in homeostatic control of energy balance; in intermediary metabolism; and in other physiologic and biochemical processes in the adult. Therefore, it is not too surprising that these enzymes are under close temporal and special regulation during development, in addition to being inducible by exogenous chemical agents. In vivo metabolism and clearance of drugs and other chemicals is the sum of many different processes including: 1) the action of many different phase I and II enzymes in the liver and extrahepatic tissues; and 2) transport systems leading to excretion in urine or bile (often termed phase III). Modern biochemical and molecular biological techniques have revealed striking differences in developmental and hormonal regulation of phase I and II enzymes and phase III transporters in different tissues. In addition, drug metabolism is affected by alterations in physiology and pathology (such as found in pregnancy and disease states) and undergo circadian, seasonal, and other types of cycling. In this chapter, changes in expression of different drug metabolizing enzymes during development are described. This is followed by sections on the effects of pathology associated with aging; on the effects of pregnancy; and on physiological cycles. Finally, information is included on development of chemical metabolism in non-mammalian species.