Weller Sasha R, Burnell John E, Aho Brandon M, Obeng Bright, Ledue Emily L, Shim Juyoung K, Hess Samuel T, Gosse Julie A
Department of Molecular and Biomedical Sciences, 5735 Hitchner, University of Maine, Orono, ME, 04469, USA.
Department of Physics and Astronomy, 5709 Bennett Hall, University of Maine, Orono, ME, 04469, USA.
Food Chem Toxicol. 2024 Apr;186:114547. doi: 10.1016/j.fct.2024.114547. Epub 2024 Feb 24.
People are exposed to high concentrations of antibacterial agent cetylpyridinium chloride (CPC) via food and personal care products, despite little published information regarding CPC effects on eukaryotes. Here, we show that low-micromolar CPC exposure, which does not cause cell death, inhibits mitochondrial ATP production in primary human keratinocytes, mouse NIH-3T3 fibroblasts, and rat RBL-2H3 immune mast cells. ATP inhibition via CPC (EC 1.7 μM) is nearly as potent as that caused by canonical mitotoxicant CCCP (EC 1.2 μM). CPC inhibition of oxygen consumption rate (OCR) tracks with that of ATP: OCR is halved due to 1.75 μM CPC in RBL-2H3 cells and 1.25 μM in primary human keratinocytes. Mitochondrial [Ca] changes can cause mitochondrial dysfunction. Here we show that CPC causes mitochondrial Ca efflux from mast cells via an ATP-inhibition mechanism. Using super-resolution microscopy (fluorescence photoactivation localization) in live cells, we have discovered that CPC causes mitochondrial nanostructural defects in live cells within 60 min, including the formation of spherical structures with donut-like cross section. This work reveals CPC as a mitotoxicant despite widespread use, highlighting the importance of further research into its toxicological safety.
尽管关于氯化十六烷基吡啶（CPC）对真核生物影响的公开信息很少，但人们通过食品和个人护理产品接触到高浓度的抗菌剂氯化十六烷基吡啶。在这里，我们表明，低微摩尔浓度的CPC暴露不会导致细胞死亡，但会抑制原代人角质形成细胞、小鼠NIH-3T3成纤维细胞和大鼠RBL-2H3免疫肥大细胞中的线粒体ATP生成。通过CPC（EC 1.7 μM）抑制ATP的效果几乎与经典线粒体毒物羰基氰化物间氯苯腙（CCCP，EC 1.2 μM）相当。CPC对氧消耗率（OCR）的抑制与ATP的抑制情况一致：在RBL-2H3细胞中，1.75 μM的CPC使OCR减半，在原代人角质形成细胞中，1.25 μM的CPC使OCR减半。线粒体[Ca]的变化可导致线粒体功能障碍。在这里，我们表明CPC通过ATP抑制机制导致肥大细胞线粒体钙外流。利用活细胞中的超分辨率显微镜（荧光光激活定位），我们发现CPC在60分钟内会导致活细胞中线粒体纳米结构缺陷，包括形成具有甜甜圈状横截面的球形结构。这项研究表明，尽管CPC被广泛使用，但它是一种线粒体毒物，凸显了进一步研究其毒理学安全性的重要性。
