The influence of 4-methylimidazole on gastrointestinal epithelial cells.

Soft drinks (non-alcoholic beverages) are a significant part of the daily diet, and the soft drinks market continues to grow annually. Since the contents of soft drinks are generally withheld and protected by law, unknown components may affect cell proliferation and the function of gastrointestinal epithelial cells. In 2017, the top-selling non-alcoholic beverage was Coca-Cola, a soft drink that contains caramel coloring. Class III and IV caramel coloring in cola contains 4-methylimidazole (4-MI), which may affect gastrointestinal epithelial cells. Therefore, the present study examined the effects of 4-MI on gastrointestinal epithelial cells (HGC-27, IEC-6, and Caco-2), which are continually exposed to 4-MI during the consumption of cola. The proliferation of HGC-27 and Caco-2, but not IEC-6, was inhibited by a short exposure to 4-MI. The physical barrier function of the epithelial cells examined was not altered by a short or long exposure to 4-MI. However, the biological barrier function, expressed by the level of P-glycoprotein, was decreased by the long exposure. Although 4-MI affected gastrointestinal epithelial cells at the concentration range used in the present study (up to 1000 µg/mL), no effects were observed at the concentrations present in soft drinks containing caramel coloring. Since the present study only examined the effects of 4-MI alone, interactions with the concomitant intake of drugs and other foods need to be considered.