Conclusions And Future Objectives

Our ever-expanding knowledge of how diet can influence the etiology of human disease is beginning to unravel how minor dietary components such as GSLs and their respective ITCs can prevent chronic diseases in humans. Epidemiological investigations coupled with the data from in vivo chemo-prevention studies show that ITCs are effective at preventing cancers especially during the initiation phase. These chemopreventive attributes appear to be associated with the induction of phase II detoxification enzymes of which in vitro studies have determined many of the signaling mechanisms involved. Members of the MAP kinases, PKC, and the association of the transcription factor Nrf2 with ARE-mediated gene expression contribute greatly to the sequence of events leading to the induction of these protective enzymes. The role of apoptosis should also be mentioned. Under circumstances when phase II detoxification enzymes are not sufficient to prevent deleterious events caused by chemical toxins, ITCs can mediate programmed cell death. Removal of neoplastic cells by ITCs could be important in the prevention of tumor formation. Indeed, work by Yang et al. (176) suggests this to be the case.

Much work, however, still remains in accessing the biological function of chemical agents derived from cruciferous vegetables. The complexity of the glucosinolate/isothiocyanate system and disease associations still requires further research, especially in the area of bacterial metabolism, antibacterial properties, bioavailability, and interactions with other phytochemical constituents. If ITCs derived from the diet can work as effectively in humans against H. pylori infections, as in vitro experiments suggest, this may well be of greater importance to the prevention of cancers and possibly heart disease than previously realized. Further investigations that encompass disease states that are associated with bacterial pathogens would be advantageous, especially in a world where antibiotic-resistant bacteria are numerous. These findings pose several questions, however. Can ITCs modulate the types of bacteria in the human gut with preference to none of the harmful colonists? Or, alternatively, can ITCs alter or prevent the metabolism of toxins by colonic bacteria, reducing their potential to damage host tissues? What are the interactions of ITCs with other phytochemicals derived from cruciferous vegetables? Several classes of phytochemicals induce separate signaling events and apoptotic cascades in mammalian cells different from those of ITCs. These interactions could well potentate the chemopreventive properties of cruciferous vegetables. This would be invaluable knowledge and pertinent to future breeding programs to improve nutritional qualities of cruciferous vegetables. Currently we still rely on using the mercapturic acid as biomarkers of ITC exposure and have yet to determine other metabolites associated with the metabolism of ITCs in humans.

Are other metabolic pathways involved? What are the metabolites present within feces and do they have any biological properties? These could all have a significant effect on human health and disease incidence. Furthermore, the ability of ITCs to induce phase II enzymes is deemed a benficial property. However, what effect does this induction have on the metabolism of pharmaceutical drugs in humans? Or, more importantly, what effect does this have on chemicals that are made more toxic by metabolism by NQO1 or GSTs? Hopefully in the future many of these questions will be answered.

The Mediterranean Diet Meltdown

The Mediterranean Diet Meltdown

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