Pharmacological perspectives on the detoxification of plant secondary metabolites: implications for ingestive behavior of herbivores.

Plant secondary metabolites (PSMs) are a major constraint to the ingestion of food by folivorous and browsing herbivores. Understanding the way in which mammalian detoxification pathways are adapted to deal with PSMs is crucial to understanding how PSMs influence ingestive behavior of herbivores and hence their fitness and the impact that they have on vegetation. Pharmacological concepts can provide insights into the relationship between the absorption and metabolic fate of PSMs and ingestive behavior. Lipophilic PSMs will be absorbed into the bloodstream and must be removed fast enough to prevent their accumulation to toxic levels. Elimination depends on their metabolism, usually by cytochrome P450 enzymes, to more polar metabolites that can be excreted by the kidney. The concentration of PSM in blood (C) is a better measure of exposure to a toxin compared to the amount ingested because there can be great variability in the rate and degree of absorption from the gut. C rises and falls depending on the relative rates of absorption and elimination. These rates depend in part on metabolic and transport processes that are saturable and liable to inhibition and induction by PSMs, indicating that complex interactions are likely. Herbivores can use diet choice and the rate and amount of PSM consumption to prevent C from reaching a critical level that produces significant adverse effects.