Institute of Applied Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, 230031, PR China; University of Science and Technology of China, Hefei, 230026, PR China; China National Tobacco Quality Supervision & Test Center, Zhengzhou, 450001, PR China.
China National Tobacco Quality Supervision & Test Center, Zhengzhou, 450001, PR China.
Environ Pollut. 2019 Jul;250:650-661. doi: 10.1016/j.envpol.2019.03.118. Epub 2019 Apr 10.
Aldehydes are well-known air pollutants and often studied alone, while co-exposure to aldehyde mixtures is more common than single aldehydes. Unfortunately, it has been very little known about the (mechanism of) combined toxicity of aldehyde mixtures. Here, formaldehyde and acrolein were selected as the typical representatives of common aldehydes, and were used to explore to get in-depth insight into the mechanism of combined toxicity of aldehyde mixtures. The NOECs (non-observed effect concentrations) are 60 μmoL/L for formaldehyde, and 0.5 μmoL/L for acrolein, so acrolein is more toxic than formaldehyde. Formaldehyde and acrolein mixtures showed significant cytotoxicity and synergistic effects in a concentration/time-dependent way on BEAS-2B cells based on acute and chronic cytotoxicity assay. Acrolein was dominant in aldehyde mixtures in inducing cytotoxicity at environmentally relevant doses because of higher toxicity. Moreover, aldehyde mixtures significantly synergistically increased the intracellular reactive oxygen species (ROS), malondialdehyde (MDA) and lactate dehydrogenase (LDH) leakage, while caused an antagonistic effects on glutathione (GSH). Besides, formaldehyde could significantly potentiated the activation of environmental stress sensitive Nrf2 pathway induced by acrolein, even at doses at which formaldehyde treatment alone had no any response. Furthermore, as the downstream components of Nrf2 pathway, catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPX) and heme oxygenase-1 (HO-1) were significantly synergistically induced by formaldehyde and acrolein mixtures. Antioxidants N-acetylcysteine and reduced glutathione could significantly suppress the acute and chronic combined cytotoxicity of acrolein and formaldehyde mixtures, and changed their interactions (synergism) on cytotoxicity. Taken together, aldehyde mixtures have higher toxicity than that expected for additivity based on single aldehydes even at environmentally relevant concentrations, and the combined cytotoxicity may be enhanced through oxidative stress and the related Nrf2 pathway. Prolonged exposure to pollutants containing aldehyde mixtures through inhalation may have more serious threat to respiratory system in animal and human.
醛类是众所周知的空气污染物，通常单独进行研究，而同时接触醛类混合物比接触单一醛类更为常见。不幸的是，人们对醛类混合物的联合毒性的（机制）知之甚少。在这里，甲醛和丙烯醛被选为常见醛类的典型代表，用于深入探讨醛类混合物联合毒性的机制。甲醛的无观察效应浓度（NOEC）为 60 μmoL/L，丙烯醛的为 0.5 μmoL/L，因此丙烯醛比甲醛更具毒性。基于急性和慢性细胞毒性测定，甲醛和丙烯醛混合物以浓度/时间依赖性方式对 BEAS-2B 细胞表现出显著的细胞毒性和协同作用。由于毒性较高，丙烯醛在环境相关剂量下在诱导细胞毒性方面在醛类混合物中占主导地位。此外，醛类混合物显著协同增加了细胞内活性氧（ROS）、丙二醛（MDA）和乳酸脱氢酶（LDH）的漏出，同时对谷胱甘肽（GSH）产生拮抗作用。此外，甲醛可显著增强丙烯醛诱导的环境应激敏感 Nrf2 途径的激活，即使在甲醛单独处理没有任何反应的剂量下也是如此。此外，作为 Nrf2 途径的下游成分，过氧化氢酶（CAT）、超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GPX）和血红素加氧酶-1（HO-1）被甲醛和丙烯醛混合物显著协同诱导。抗氧化剂 N-乙酰半胱氨酸和还原型谷胱甘肽可显著抑制丙烯醛和甲醛混合物的急性和慢性联合细胞毒性，并改变它们在细胞毒性方面的相互作用（协同作用）。综上所述，即使在环境相关浓度下，醛类混合物的毒性也高于基于单一醛类的预期毒性，并且联合细胞毒性可能通过氧化应激和相关的 Nrf2 途径增强。通过吸入长期接触含有醛类混合物的污染物可能对动物和人类的呼吸系统造成更严重的威胁。
