The influence of in vitro simulated digestion process on alpha-dicarbonyl compound cytotoxicity

alpha-Dicarbonyl compounds are intermediate substances occurring in thermally treated foods as reaction products of caramelization, Maillard reaction, and lipid peroxidation, in fermented foods and beverages, where are produced by microorganism metabolisms, in plants, produced in response to stress conditions, in water, in tobacco smoke, and in medical products (peritoneal dialysis fluids). Glyoxal (G) and methylglyoxal (MG) can be produced also by many strains of bacteria present in the intestinal tract, and are endogenous compounds because are human physiological metabolites. Alpha-Oxoaldehydes are highly reactive alkilating agents, that have been found to rapidly modify side chains of protein and form reversible Schiff’s base that after subsequent rearrangements, oxidations and dehydratations, yields relatively stable Amadori products, known as Maillard reaction products (MRPs) if occur in foods, or advanced glycation products (AGEs) if are endogenously formed. Recent publications reported that both alpha-dicarbonyl compounds and AGEs induced several cellular damages, mainly attributed to their interaction with essential cellular macromolecules, leading to the alteration in structure and function of some kind of cells. In recent years the role of exogenous alpha-dicarbonyl compounds in gastrointestinal tract is under investigation to understand whether excess consumption of such dietary compounds might be a risk for human health. Nevertheless, to our knowledge, the influence of the digestion process on food derived alpha-dicarbonyl compounds has not been investigated. Therefore, a mixture of alpha-dicarbonyl compounds, commonly occurring in foods (G, MG and diacetyl), before and after in vitro simulated gastrointestinal digestion process, was evaluated for its ability to induce cytotoxicity against three different cultured cell lines and to inhibit the function of selected enzymes responsible for DNA repair in human cells. Then these properties were correlated both to the alpha-dicarbonyl compound content (determined by a validated RP-HPLC-DAD method) before and after digestion and with the digestive enzyme carbonylation induced by alpha-dicarbonyl compounds. The digested alpha-dicarbonyl mixtures was found to contain compound(s) with apparent selective in vitro antiproliferative activity against colon cancer cells, but not other cell lines. Overall, the results showed that digested alpha-dicarbonyl compounds should not be cytotoxic towards normal cells, but may display specific anticancer activity.