Formation of oleic acid/histidine and oleic acid/glutamine reaction products under high-temperature and their effects on THP-1-derived macrophages

This study investigated the formation and cytotoxic effects of reaction products generated from oleic acid with histidine or glutamine under high-temperature model reaction conditions. The resulting oleic acid–histidine derivatives (OHDs) and oleic acid–glutamine derivatives (OGDs) were isolated and characterized by gas chromatography-mass spectrometry, transmission electron microscopy (TEM), Fourier transform infrared spectroscopy, X-ray diffraction, and dynamic light scattering. The results suggested the formation of distinct chemical products and nanostructured organic materials, as evidenced by TEM analysis showing nanoscale structures ranging from 5 to 18 nm for OGDs and 2–20 nm for OHDs, whereas dynamic light scattering revealed average particle sizes of 103 nm and 85 nm, respectively. In vitro exposure of THP-1-derived macrophages to OHDs and OGDs induced marked cytotoxicity. At 400 µg/mL, OGD treatment resulted in cell death rates of 60.46% and 64.67%, whereas OHD treatment had death rates of 43.05% and 40.49% after 24 and 48 h, respectively. These findings indicate that high-temperature processing of fatty acid–amino acid mixtures can generate potentially harmful nanostructured organic materials. The study highlights a potential food safety concern associated with overheated or charred foods and underscores the importance of evaluating cooking practices that may promote the formation of hazardous compounds.