Comparative Effects of Acrolein and Glyoxal on Redox Homeostasis, Antioxidant Defense and Membrane Properties in Human Peripheral Blood Mononuclear Cells: An In Vitro Study

Acrolein (ACR) and glyoxal (GO) are highly reactive carbonyls originating from endogenous metabolism, environmental pollution, and thermal food processing. This study compares the toxic mechanisms and redox effects of a 24 h exposure to ACR (30, 60, 90 µM) and GO (2, 5, 10 mM) in PBMCs. We assessed cell viability, lipid membrane fluidity, reactive oxygen/nitrogen species (ROS/RNS), free protein functional groups, reduced glutathione (GSH), non-enzymatic antioxidant capacity (NEAC), antioxidant enzyme activity (CAT, GPx), and protein expression levels (CAT, SOD1). Both aldehydes reduced viability in a concentration-dependent manner (ACR was over 30-fold more toxic than GO based on viability curves). These toxins increased membrane fluidity near the surface, while GO also altered the hydrophobic core. Both triggered a profound accumulation of ROS/RNS. At specific dose thresholds (ACR ≥ 60 µM; GO ≥ 5 mM), both toxins depleted GSH and NEAC, decreased protein thiol/amino groups, and suppressed CAT/GPx catalytic activity and CAT/SOD1 protein expression. In conclusion, ACR emerged as a markedly more potent inducer of oxidative stress and antioxidant failure than GO in PBMCs, disrupting both non-enzymatic (GSH, NEAC) and enzymatic (CAT, GPx, SOD1) defenses. These results support prioritizing ACR in exposure risk assessments and developing biomarkers of carbonyl-induced immune dysfunction.