Impact of parabens, individually and in mixture, on human neutrophil oxidative burst under physiological and hyperglycemic conditions.

Parabens are a family of alkyl esters of 4-hydroxybenzoic acid (4-HB), widely used as antimicrobial agents in various industries, including cosmetics, pharmaceuticals, and food. However, concerns have been raised regarding their potential to disrupt the endocrine system and contribute to chronic inflammation, leading to their classification as endocrine-disrupting chemicals. Neutrophils play a central role in innate immune responses, and can be influenced by the surrounding metabolic environment, including glucose levels. Hyperglycemia, characterized by elevated plasma glucose levels, is a common feature of metabolic disorders. Therefore, this study explored the impact of common parabens - namely methylparaben (MeP), ethylparaben (EtP), propylparaben (PrP), butylparaben (BuP) and their metabolite 4-HB, tested alone or combined at different ratios, on human neutrophils' oxidative burst under physiological and hyperglycemic conditions. Results evidenced that single parabens induced neutrophils' oxidative burst, through activation of phospholipase C (PLC) and protein kinase C (PKC), leading to NADPH oxidase and myeloperoxidase (MPO) activation. No effects were observed following exposure to 4-HB. Additionally, paraben mixtures, tested at total concentrations up to 100 μM, predominantly exhibited additive effects under both physiological and hyperglycemic conditions. These findings highlight the potential of parabens, particularly in mixtures, to modulate neutrophil oxidative responses, reinforcing the need to consider combined chemical exposure in toxicological risk assessment.