title: Prevention of spontaneous and cyclophosphamide-induced diabetes in non-obese diabetic (NOD) mice with oral 2-acetyl-4-tetrahydroxybutylimidazole (THI), a component of caramel colouring III.
abstract: The effect of oral administration of THI, a compound present in ammonia caramel food colouring, was studied in spontaneous and induced murine diabetes mellitus. Continuous administration of THI at 400 ppm in drinking water reduced the prevalence of spontaneous diabetes in female NOD/Lt mice from 63% in untreated controls to 8% in treated animals. Since cyclophosphamide (CP) accelerates and intensifies diabetes in NOD mice, we also studied the effect of THI in this model. Diabetes incidence was reduced from 100% in mice given only CP to 13-14% in mice given THI either concurrently or from 14 days previously. Histologically, THI greatly reduced the severity of insulitis. As measured by flow cytometry, all THI-treated mice had a 60-80% reduction in splenic CD4+ and CD8+ T cells. THI-treated mice showed no untoward effects and specifically no weight loss, or pathological changes in their livers, kidneys or lungs. However, there was moderate atrophy of the thymus cortex. THI is a small imidazole-containing compound with structural similarity to histamine and urocanic acid, both known to have immunosuppressive properties. It is a widely used food additive with no known long-term toxic effects at low dosage. Thus, THI could be a useful immunosuppressive agent.
authors.affiliation: Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
authors.forename: T E
authors.initials: TE
authors.lastname: Mandel
authors.forename: M
authors.initials: M
authors.lastname: Koulmanda
authors.forename: I R
authors.initials: IR
authors.lastname: Mackay
mesh_terms: D000284:Administration, Oral; D000818:Animals; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D003520:Cyclophosphamide; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000517:prevention & control*; D005260:Female; D005434:Flow Cytometry; D007093:Imidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D008231:Lymphopenia / Q000139:chemically induced; D051379:Mice; D016688:Mice, Inbred NOD; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D013950:Thymus Gland / Q000187:drug effects
chemical_list: D015704:CD4 Antigens; D016827:CD8 Antigens; D007093:Imidazoles; D003520:Cyclophosphamide; C049929:2-acetyl-4(5)-tetrahydroxybutylimidazole