Aging Aging

Xenobiotic-Metabolizing Enzymes 1198Xenobiotic-Metabolizing Enzyme Systemsand AgingChristopher R. Barnett and Costas Ioannides1. IntroductionThe human body is continuously exposed to a wide array of structurallydiverse chemicals. Such exposure occurs even at the fetal stage as almost allchemicals that are present in the mother’s blood can readily cross the placentaand reach the fetus. Some of these chemicals are ingested voluntarily, for example,medicines and food additives, but the vast majority are taken involuntarily,as environmental contaminants present in the air or in the occupationalenvironment. Undoubtedly, the most important source of such chemicals is thediet, and many dietary constituents have been shown to induce many forms oftoxicity including cancer (1). Exposure to chemicals is thus inevitable andunavoidable. The body cannot exploit these chemicals either to generate energyor transform them to building blocks and consequently its response is to riditself of their presence. This chapter discusses the role of drug-metabolizingenzyme systems in this process and the effects of age. The measurement ofdrug-metabolizing activities is of increasing importance in the safety evaluationof drugs in humans. This chapter describes the use of alkylphenoxazonederivatives for investigating selected activities of drug-metabolizing enzymes.Chemicals that reach the systemic circulation and are distributed throughoutthe body are generally lipophilic, a property that allows them to traverse thevarious cellular membranes. Such lipophilic chemicals are also difficult toexcrete through the kidney and bile. Consequently, to facilitate their elimination,the body converts them to hydrophilic metabolites, which are much easierto excrete. Furthermore, such metabolism terminates any biological activitythat may be manifested by these chemicals, as the products of metabolism arebiologically inactive, being unable to interact with the receptors for which theFrom: Methods in Molecular Medicine, Vol. 38: Aging Methods and ProtocolsEdited by: Y. A. Barnett and C. R. Barnett © Humana Press Inc., Totowa, NJ119