Influence of non-nutrient plant components on biotransformation enzymes

Plant foods contain numerous non-nutritive substances which exert biological activity. Most attention has been focused on the anticarcinogenic effects of these compounds. Many of the mechanisms involved include induction or inhibition of biotransformation enzymes. Each individual has its own isoenzyme pattern for the various drug-metabolizing enzymes. The multiplicity of these enzymes results in differential responses to dietary constituents. A substance may increase the level of a certain P450, and decrease the level of another. Although this complicates matters considerably, it also offers the possibility of specifically influencing biotransformation directed at a particular compound, e.g., a cytostatic agent. Using the important class of the glutathione S-transferase (GST) as an example, the various phenotypic and genetic origins of interindividual variation are described. Genetic variation is especially important for the mu and thetra class enzymes. The induction of individual isoenzymes of the GST has been studied in man rat. It was shown that the changes in the GST isoenzyme pattern induced by Brussels sprouts in rat liver and intestine were very similar to that caused by administration of ally isothiocyanate, and not to that resulting from goitrin. In man Brussels sprouts led to induction of GST alpha only. A number of naturally occurring catechols, or more likely the quinones derived from them, are effective irreversible inhibitors of GST. Eugenol, for instance, lowers GST activity in man. A second class of compounds which shows promise are alpha, beta-unsaturated aldehydes and ketones. A number of naturally occurring representatives of this class inhibit GST pi irreversibly, and ethacrynic acid, a drug with a similar reactive moiety in its structure, has already been shown to be quite useful to inhibit GST activity in cellular systems. Several approaches for future studies on the effects of dietary constituents are indicated: 1) further studies on the mechanisms of induction and inhibition of biotransformation enzymes: 2) careful studies using human volunteers, where the effects can be studied in isolation as much as possible; 3) studies of the disposition and kinetics of the dietary constituents themselves, to assess the relevance of inducing agents in food for the day-to-day human situation.