Noxious effects of selected food-occurring oxidized amino acids on differentiated CACO-2 intestinal human cells

Area of Science:

• Biochemistry
• Cell Biology
• Toxicology

Background:

• Oxidized amino acids are present in food and may pose health risks.
• Understanding their impact on intestinal cells is crucial for food safety.

Purpose of the Study:

• To investigate the harmful effects of specific food-occurring oxidized amino acids on differentiated CACO-2 cells.
• To elucidate the mechanisms underlying their toxicity, including oxidative stress and apoptosis.

Main Methods:

• Differentiated CACO-2 cells were exposed to food-relevant doses (200 μM) of aminoadipic acid (AAA), dityrosine (DTYR), L-kynurenine (KN), kynurenic acid (KA), and 3-nitrotyrosine (3NT).
• Cellular responses were assessed using flow cytometry, quantifying glutathione (GSH) levels and allysine accretion.
• Apoptosis, necrosis, reactive oxygen species (ROS) generation, and cell cycle arrest were evaluated.

Main Results:

• All tested oxidized amino acids induced apoptosis in CACO-2 cells.
• AAA, KN, and KA triggered significant ROS generation and oxidative stress, leading to GSH depletion and allysine accumulation.
• DTYR and 3NT induced apoptosis and necrosis via ROS-independent pathways.
• KN and KA also caused cell cycle arrest.

Conclusions:

• Food-occurring oxidized amino acids exhibit varying toxic mechanisms, including oxidative stress and apoptosis.
• The findings underscore the potential health hazards associated with consuming oxidized proteins and amino acids.
• Further molecular investigations are warranted to fully understand these toxic effects.