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2-Acetyl-4-((1R,2S,3R)-1,2,3,4-tetrahydroxybutyl)imidazole (THI) is observed as a minor contaminant in caramel food colourings (E 150c). Feeding experiments with rodents have revealed a significant lymphopenic effect that has been linked to the presence of THI in these food colourings. Pyridoxal kinase inhibition by THI has been suggested, but not demonstrated, as a mode of action as it leads to lowered levels of pyridoxal-5'-phosphate, which are known to cause lymphopenia. Recently, THI was also shown to inhibit sphingosine-1-phosphate lyase causing comparable immunosuppressive effects and derivatives of THI are being developed for the treatment of rheumatoid arthritis in humans. Interestingly, sphingosine-1-phosphate lyase activity depends on pyridoxal-5'-phosphate, which in turn is provided by pyridoxal kinase. This report shows that THI does inhibit pyridoxal kinase with competitive and mixed-type non-competitive behaviour towards its two substrates, pyridoxal and ATP, respectively. The corresponding inhibition constants are in the low millimolar range.

Although fast green (FG) is widely used as food colorant by the cosmetics and drug industries, there is no evidence about whether FG affects leukocytes. The aim was to investigate the effect of FG on leukocytes. Male albino mice were subdivided into five equal groups: four of them were given 125, 250, 375 and 500 mg kg(-1) bw day(-1) FG in drinking water for 44 days. The fifth (control group) was given pure water only. During the experimental period changes in body weight, lymphoid organs weight (absolute and relative) as well as the total count and viability of lymphoid cells for the treated groups showed that FG was an immunotoxic agent. The structural effects induced by FG on thymocytes and splenocytes were investigated through measurements of their dielectric spectra in the frequency range 20-100,000 Hz. The estimated dielectric parameters of the treated groups reflected the changes occurring to lymphocytes by FG administration and indicated that FG dye is an immunotoxic agent. It is shown that the dielectric methodology can be used for the identification of lymphocyte modification induced by food colorants.

Synthetic or natural food dyes are typical xenobiotics, as are drugs and pollutants. After ingestion, part of these dyes may be absorbed and metabolized by phase I and II drug-metabolizing enzymes and excreted by transporters of phase III enzymes. However, there is little information regarding the metabolism of these dyes. It was investigated whether these dyes are substrates for CYP2A6 and UDP-glucuronosyltransferase (UGT). The in vitro inhibition of drug-metabolizing enzymes by these dyes was also examined. The synthetic food dyes studied were amaranth (food red no. 2), erythrosine B (food red no. 3), allura red (food red no. 40), new coccine (food red no. 102), acid red (food red no. 106), tartrazine (food Yellow no. 4), sunset yellow FCF (food yellow no. 5), brilliant blue FCF (food blue no. 1), and indigo carmine (food blue no. 2). The natural additive dyes studied were extracts from purple sweet potato, purple corn, cochineal, monascus, grape skin, elderberry, red beet, gardenia, and curthamus. Data confirmed that these dyes were not substrates for CYP2A6, UGT1A6, and UGT2B7. Only indigo carmine inhibited CYP2A6 in a noncompetitive manner, while erythrosine B inhibited UGT1A6 (glucuronidation of p-nitrophenol) and UGT2B7 (glucuronidation of androsterone). In the natural additive dyes just listed, only monascus inhibited UGT1A6 and UGT2B7.

Rubropunctatin (1), monascorubrin (2), monascin (3) and ankaflavin (4) were purified from the mycelium of Monascus purpureus by flash chromatography on silica gel or reversed phase. Their embryotoxicity towards chicken embryos decreased in the order 2 > 1 > 3 > 4. The lower homologues 1 and 3 exhibited teratogenic effects on these organisms. Significant antibiotic activities against Bacillus subtilis and Candida pseudotropicalis were found with compounds 1 and 2. Immunosuppressive activity on mouse T-splenocytes was most pronounced with compounds 3 and 4. None of the compounds showed significant cytotoxic activity towards rat hepatocytes in vitro. Incubation of resting cells of M. purpureus with glycine afforded the dark-red compounds 5 and 6 where the pyran moiety of 1 and 2 changed into the N-substituted dihydropyridine moiety by replacement of the O-atom by the amino group of glycine. Compounds 5 and 6 were less biologically active than the major pigments 1-4.

Eleven organic synthetic dyes, currently or formerly used as food colours in Brazil, were tested to determine their effect on mitochondrial respiration in mitochondria isolated from rat liver and kidney. The compounds tested were: Erythrosine, Ponceau 4R, Allura Red, Sunset yellow, Tartrazine, Amaranth, Brilliant Blue, Blue, Fast Red E, Orange GGN and Scarlet GN. All food colours tested inhibited mitochondrial respiration (State III respiration, uncoupled) supported either by alpha-ketoglutarate or succinate. This inhibition varied largely, e.g. from 100% to 16% for Erythrosine and Tartrazine respectively, at a concentration of 0.1 mg food colour per mitochondrial protein. Both rat liver and kidney mitochondria showed similar patterns of inhibition among the food colours tested. This effect was dose related and the concentration to give 50% inhibition was determined for some of the dyes. The xanthene dye Erythrosine, which showed the strongest effect, was selected for further investigation on mitochondria in vivo.