In Vitro Evaluation of the Toxicological Profile and Oxidative Stress of Relevant Diet-Related Advanced Glycation End Products and Related 1,2-Dicarbonyls.
Vanesa CepasFriederike ManigJuan Carlos MayoMichael HellwigDebora CollottaValentina SanmartinoRebeca Carrocera-PumarinoMassimo CollinoThomas HenleRosa María SainzPublished in: Oxidative medicine and cellular longevity (2021)
During food processing and storage, and in tissues and fluids under physiological conditions, the Maillard reaction occurs. During this reaction, reactive 1,2-dicarbonyl compounds arise as intermediates that undergo further reactions to form advanced glycation end products (AGEs). Diet is the primary source of exogenous AGEs. Endogenously formed AGEs have been proposed as a risk factor in the pathogenesis of diet-related diseases such as diabetes, insulin resistance, cardiovascular diseases, or chronic disease. AGEs may differently contribute to the diet-related exacerbation of oxidative stress, inflammation, and protein modifications. Here, to understand the contribution of each compound, we tested individually, for the first time, the effect of five 1,2-dicarbonyl compounds 3-deoxyglucosone (3-DG), 3-deoxygalactosone (3-DGal), 3,4-dideoxyglucosone-3-ene (3,4-DGE), glyoxal (GO), and methylglyoxal (MGO) and four different glycated amino acids N-ε-(carboxyethyl)lysine (CEL), N-ε-(carboxymethyl)lysine (CML), methylglyoxal-derived hydroimidazolone-1 (MG-H1), and pyrraline (Pyrr) in a cell line of human keratinocytes (HaCaT). We found that most of the glycated amino acids, i.e., CEL, CML, and MG-H1, did not show any cytotoxicity. At the same time, 1,2-dicarbonyl compounds 3-DGal, 3,4-DGE, GO, and MGO increased the production of reactive oxygen species and induced cell death. MGO induced cell death by apoptosis, whereas 3-DGal and 3,4-DGE induced nuclear translocation of the proinflammatory NF-κB transcription pathway, and the activation of the pyroptosis-related NLRP3 inflammasome cascade. Overall, these results demonstrate the higher toxic impact of 1,2-dicarbonyl compounds on mucosal epithelial cells when compared to glycated amino acids and the selective activation of intracellular signaling pathways involved in the crosstalk mechanisms linking oxidative stress to excessive inflammation.
Keyphrases
- oxidative stress
- diabetic rats
- amino acid
- cell death
- nlrp inflammasome
- insulin resistance
- high glucose
- signaling pathway
- cardiovascular disease
- reactive oxygen species
- drug induced
- induced apoptosis
- physical activity
- type diabetes
- ischemia reperfusion injury
- endothelial cells
- dna damage
- adipose tissue
- skeletal muscle
- epithelial mesenchymal transition
- high fat diet
- immune response
- small molecule
- mechanical ventilation
- cardiovascular events
- intensive care unit
- heat stress
- climate change
- stress induced
- polycystic ovary syndrome