Sequestration of acrylamide as amino acid-acrylamide adducts mitigates cellular stress in human gastrointestinal cell lines

Acrylamide (ACR) present in starchy and cereal-based heat-processed foods raises a global health concern. While amino acids (AAs) have been suggested as effective scavengers of acrylamide, there is a dearth of information about the cellular response to amino acid-acrylamide (AA-ACR) adducts. In this work, we conducted a detailed comparison of the effects of ACR <i>versus</i> AA-ACR adducts on two human gastrointestinal cell lines, namely, Caco-2 and HCT-15. Adducts of lysine, glycine, cysteine, and methionine with ACR were prepared under optimised reaction conditions and characterized by a combination of ESI-MS and MS/MS. Exposure of Caco-2 and HCT-15 to these adducts resulted in significant reduction in the formation of reactive oxygen species (ROS) and the prevention of abnormal accumulation of the cells in the G1 phase. The analysis of apoptosis and necrosis in the cell lines treated with AA-ACR clearly indicated the ability of AAs to sequester ACR and block oxidative stress induction that would otherwise be observed, completely precluding apoptosis and necrosis. Sequestration of ACR with each of the four AAs prevented the loss of mitochondrial membrane potential and the induction of autophagy that would otherwise occur upon exposure to ACR. The hitherto untested behaviour of human gastrointestinal cells towards AA-ACR presented in this work supports the application of AAs for the mitigation of ACR in foods.