Fig. 2.

The functional relationship between the AhR ligands and the regulatory roles of this receptor in physiology and pathophysiology. Synthetic ligands such as Halogenated Aromatic Hydrocarbons (HAHs) such as PCBs (“Polychlorobiphenyls”) and PCDD (polychlorinateddibenzo-para-dioxins) or PAHs (Polycyclic Aromatic Hydrocarbons) which include benzo (a) pyrene (B(a)P) or 3-methylcholanthrene (3-MC) were among the first molecules to be identified as AhR ligands. These molecules are present in the air or in foods as complex mixtures, they are very stable; some may accumulate in the body (TCDD has a half-life of about seven years in humans) and they are powerful inducers of AhR [80]. Dioxins or PCBs are highly soluble in fats and can, therefore, reach high concentrations in fatty foods such as dairy products, fishes, meats and seafood. More recently, ligands of natural origins (food and endogenous ligands) such as flavonoids or indole derivatives also have been characterized as AhR ligands. Flavonoids are found in fruits and vegetables and represent the most abundant class of polyphenols. Among them, quercetin and resveratrol activate the AhR [8], [81] and exert both agonist and antagonistic effects. Indoles such as indole-3-carbinol (I3C), which are derived from cruciferous plants such as broccoli or Brussels sprouts, are reported to have anti-cancer properties. Part of the effects of I3C occurs via activation of the AhR [82]. In addition, physiological endogenous ligands of the AhR such as indole amino acid metabolites (tryptophan, tryptamine, indole acetic acid) recently have been characterized. A photoproduct of tryptophan also has been identified through structural and chromatographic studies [83]: FICZ (6-formylindolo [3,2-b] carbazole) [84]. Indirubin and indigo represent another group of indoles [85] which are detected in human urine under normal physiological conditions and, therefore, are present in our organisms, and are strong inducers of the AhR [85], [86]. Physiological ligands also include metabolites of arachidonic acid (lipoxin A4, some prostaglandins (PGG2)) [87], [88], tetrapyroles (bilirubin, a degradation product), heme and biliverdin [89]).