Kaczmarska Izabela, Mokra Katarzyna, Michałowicz Jaromir
Doctoral School of Exact and Natural Sciences, University of Lodz, Matejki 21/23 St., 90-237 Lodz, Poland.
Department of Biophysics of Environmental Pollution, Faculty of Biology and Environmental Protection, University of Lodz, 141/143 Pomorska St., 90-236 Lodz, Poland.
Int J Mol Sci. 2025 Jun 5;26(11):5408. doi: 10.3390/ijms26115408.
Perfluorooctanoic acid (PFOA) and its short-chain substitutes, perfluorohexanoic acid (PFHxA) and perfluorobutanoic acid (PFBA), are persistent environmental pollutants associated with widespread human exposure through occupational and environmental routes. The aim of this was to investigate the effects of PFOA, PFHxA, and PFBA on the intracellular level of adenosine-5'-triphosphate (ATP) in human peripheral blood mononuclear cells (PBMCs) and their viability, size, and granularity. Moreover, oxidative and nitrosative stress was assessed based on the levels of reactive oxygen species (ROS), reactive nitrogen species (RNS), and highly reactive oxygen species (hROS, mainly hydroxyl radical). Finally, oxidative damage to protein and lipids in PBMCs was measured. The cells were incubated for 1 h and 24 h at concentrations correlated to human occupational and environmental exposure (0.001-200 µg/mL) to the substances. Our findings indicate that PFOA and its short-chain analogs cause different effects in human PBMCs. PFOA induced statistically significant alterations almost in all studied parameters, substantially decreasing cell viability and ATP level and altering the size and granularity of tested cells; in contrast, PFHxA and PFBA induced significant changes only at some studied parameters. PFOA also induced a notable increase in intracellular ROS and RNS levels, which suggest that both oxidative stress and nitrosative stress influence its cytotoxic potential. Interestingly, the shortest-chain compound, PFBA, induced changes that were not observed for PFHxA. This suggests that the length of the chain determines the triggering of certain alterations in PBMCs. Importantly, the changes were noted at concentrations corresponding to those associated with occupational exposure. These findings contribute to our understanding of the immunotoxicity of PFOA and its substitutes, indicating the potential health risks associated with chronic exposure, particularly in populations with occupational exposure or high environmental PFOA burdens.
全氟辛酸（PFOA）及其短链替代物全氟己酸（PFHxA）和全氟丁酸（PFBA）是持久性环境污染物，通过职业和环境途径导致人类广泛接触。本研究的目的是调查PFOA、PFHxA和PFBA对人外周血单核细胞（PBMCs）细胞内三磷酸腺苷（ATP）水平及其活力、大小和颗粒度的影响。此外，基于活性氧（ROS）、活性氮（RNS）和高活性氧（hROS，主要是羟基自由基）水平评估氧化应激和亚硝化应激。最后，检测PBMCs中蛋白质和脂质的氧化损伤。将细胞在与人类职业和环境接触这些物质相关的浓度（0.001 - 200μg/mL）下孵育1小时和24小时。我们的研究结果表明，PFOA及其短链类似物在人PBMCs中产生不同影响。PFOA几乎在所有研究参数中均诱导出具有统计学意义的变化，显著降低细胞活力和ATP水平，并改变受试细胞的大小和颗粒度；相比之下，PFHxA和PFBA仅在一些研究参数中诱导出显著变化。PFOA还诱导细胞内ROS和RNS水平显著升高，这表明氧化应激和亚硝化应激均影响其细胞毒性潜力。有趣的是，最短链化合物PFBA诱导出PFHxA未观察到的变化。这表明链的长度决定了PBMCs中某些变化的触发。重要的是，在与职业接触相关的浓度下观察到了这些变化。这些发现有助于我们理解PFOA及其替代物的免疫毒性，表明与慢性接触相关的潜在健康风险，特别是在职业接触人群或环境中PFOA负担高的人群中。
