Evaluation of the interactions of herbal dietary supplements with molecular targets at the intestinal level : a first step toward risk assessment
(2011)
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- (en) Since a few years, nutritional habits are changing. We assist to a growing use of herbal dietary supplements, which are sold freely without medical advice, despite their recognized physiological effects. Little is known about the safety of these products. The need for relevant toxicological data, generated at plausible exposure, is therefore encouraging researchers to develop new approaches of risk assessment, adapted to the specificities of herbal dietary supplements, as well as high-throughput in vitro screening tools. Due its high potential of first-pass metabolization, the small intestine, which is exposed to high doses of diverse dietary compounds, plays a key role in food safety. In a first part of the work, a review of the interactions between dietary compounds, including contaminants and phytochemicals, and main first-pass biotransformation enzymes permitted to highlight the major role of cytochrome P-450 (CYP), and especially CYP1A1, in determining bioavailability and potential toxicity at the intestinal level. We therefore dedicated the first experimental part of the work to the study of the modulation of CYP1A1 activity by Ginkgo biloba, a widely used herbal dietary supplement, and by its major active compounds, alone or in mixtures, in the human intestinal Caco-2 cells, at realistic exposure. Ginkgo biloba extracts demonstrated to strongly enhance CYP1A1 activity, suggesting unsuspected side effects for consumers. In a second experimental part, on the basis of our previous experience with Caco-2 cells, we set up an original methodology, involving four distinct in vitro tools packed together in a toolbox, and permitting to easily investigate relevant toxicological effects of dietary compounds at realistic human exposure, with a special interest for the intestinal compartment. This method was validated with four well-known dietary contaminants showing human health concern (ochratoxin A, deoxynivalenol, imazalil and benomyl), in order to be applied in the future to other less studied chemicals, such as active compounds of herbal dietary supplements. Given the necessity to implement our knowledge in the safety of herbal dietary supplements, we have ended up our work by discussing the application of the toolbox as a first step for the risk assessment of these products. Taken as a whole, this thesis opens doors towards the identification of priorities for risk assessment studies and emphasizes the relevance of in vitro tools in food safety.
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Ribonnet, L. (2011). Evaluation of the interactions of herbal dietary supplements with molecular targets at the intestinal level : a first step toward risk assessment. https://hdl.handle.net/2078.5/69396