Safety issues of methylglyoxal and potential scavengers

The health safety of methylglyoxal (MGO) has been recognized as a key issue owing to its ultra-high reactivity toward some key biomolecules such as amino acids, proteins, DNA, sulfhydryl- and basic nitrogen-containing compounds, including amino-bearing neurotransmitters. In this review, we have summarized the endo- and exogenous sources of MGO and its accumulation inside the body due to high intake, abnormal glucose metabolism and or malfunctioning glyoxalases, and review the debate concerning the adverse functionality of MGO ingested from foods. Higher than normal concentrations of MGO in the circulatory system and tissues have been found to be closely associated with the production of advanced glycation end products (AGEs), increased oxidative stress, elevated inflammation and RAGE (AGE receptors) activity, which subsequently progresses to a pathological stage of human health, such as diabetes complications, cancer, cardiovascular and degenerative diseases. Having illustrated the mechanisms of MGO trapping in vivo, we advocate the development of efficient and efficacious MGO scavengers, either assisting or enhancing the activity of endogenous glyoxalases to facilitate MGO removal, or providing phytochemicals and functional foods containing them, or pharmaceuticals to irreversibly bind MGO and thus form MGO-complexes that are cleared from the body.