Interaction of the Isothiocyanate Sulforaphane with Drug Disposition and Metabolism: Pharmacological and Toxicological Implications
Isothiocyanates (ITCs) are sulfur-containing compounds that are broadly distributed among cruciferous vegetables such as cabbages and broccoli. The consumption of ITCs is expected to rise due to the use of dietary supplements and public health initiatives promoting the consumption of more fruits and vegetables. Sulforaphane (SFN) is by far the most widely studied and characterized ITC. SFN is extensively metabolized and can therefore compete with other substrates of Phases I, II, III enzymes and transporters. In addition, it has an unusually high potency as an inducer of phase II enzymes and regulates the expression and function of different cytochrome P-450 genes. Such effects can be beneficial and may indicate a mechanism for the preventive role that SFN is believed to play against the degenerative events of aging and chronic diseases. Furthermore, these gene induction effects and the interaction with detoxification responses can modify bioavailability and in vivo bioactivity of drugs. This review will discuss 1) the metabolism of ITCs using SFN as an example, 2) inhibition of drug metabolism by SFN, and 3) induction of drug metabolizing enzymes by SFN. The potential pharmacological and toxicological implications of these effects on drug metabolism will also be discussed.
Keywords: Sulforaphane, isothiocyanates, drug metabolizing enzymes, glutathione-S-transferase, NF-E2-related factor 2, cytochrome P-450, antioxidant activity, cancer chemotherapy
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