Studies on mechanism of free Nε‐(carboxymethyl)lysine‐induced toxic injury in mice

Abstract

Nε‐(carboxymethyl)lysine (CML), which is a compound produced when food is processed, has aroused concern in recent years because of its potentially dangerous effects. This study aimed to investigate the mechanism of free CML‐induced toxic injury in mice. The inflammatory cytokine tumor necrosis factor‐α, transforming growth factor‐β, vascular cell adhesion molecule‐1 mRNA expression levels of CML‐infected mice liver and kidney tissues significantly increased. While CML receptor—receptor for advanced glycation end products (RAGE) protein expression in male mice liver tissue had a more significant change than the control group, there was no significant difference in other dose groups compared with the control group. In conclusion, the foodborne free CML can be induced by oxidative stress and immune response to liver and kidney tissue injury in mice. Additionally, the free CML may also bind to RAGE, which activates the downstream inflammatory pathway.

Redox Signaling and Advanced Glycation Endproducts (AGEs) in Diet-Related Diseases

“…It engages different ligands, not only AGEs, but also the amyloid β peptide, S100/calgranulin protein, HMGB1, and LPS, ultimately leading to an alteration in gene expression [15][16][17][18]. Recent studies have shown that Ne(carboxymethyl)lysine (CML) adducts of proteins, the most frequent type of AGEs found in vivo, interact with RAGE to activate signal transduction pathways [19,20], ultimately leading to the expression of proinflammatory genes [21]. Thus, it has been shown that treating cells with AGEs produces a rapid increase in both mRNA and protein levels of RAGE [22] which is suppressed after pretreatment with the anti-RAGE antibody [23].…”

CIGB-258 Exerts Potent Anti-Inflammatory Activity against Carboxymethyllysine-Induced Acute Inflammation in Hyperlipidemic Zebrafish via the Protection of Apolipoprotein A-I

“…The anti-inflammatory activity of CIGB-258 might have originated partially from the structural and functional stabilization of HDLs against CML-induced glycation of HDLs and modification [ 21 ]. Although the CML is a relatively stable advanced glycated end (AGE) product, many previous papers suggested its neurotoxicity and oral toxicity [ 22 , 23 , 24 ]. The CML can bind to tissue proteins [ 25 ] and accumulate in animal tissues after 12 weeks of oral administration via glycoxidation and lipid peroxidation [ 26 ].…”

Bioactivity-guided isolation of the major anthocyanin fromLycium ruthenicumMurr. fruit and its antioxidant activity and neuroprotective effectsin vitroandin vivo

“…Several studies indicated that AGEs including CML induced ROS production, resulting in oxidative stress damage in cells. 29,30 In order to investigate the effects of Pn3G5G and/or CML on the oxidative stress, we detected the ROS level and malondialdehyde (MDA) concentration (a marker of lipid peroxidation (LPO)) in Neuro-2a cells. As displayed in Fig.…”