Chen Yi-Chun, Andrew Lin Kun-Yi, Chen Ku-Fan, Jiang Xin-Yu, Lin Chia-Hua
Department of Biotechnology, National Formosa University, Yunlin, 63208, Taiwan; Department of Civil Engineering, National Chi Nan University, Nantou, 54561, Taiwan.
Department of Environmental Engineering, National Chung Hsing University, Taichung, 40227, Taiwan.
Environ Pollut. 2021 Mar 15;273:116528. doi: 10.1016/j.envpol.2021.116528. Epub 2021 Jan 18.
HKUST-1 is currently studied for a very diverse range of applications. Despite its exciting potential, significant concerns remain regarding the safety of HKUST-1. Therefore, human embryonic kidney 293 (HEK293) cells were used to verify the renal toxicity of HKUST-1. In this study, HKUST-1 induced concentration-dependent cytotoxic effects in HEK293 cells. The depolarization of mitochondrial membrane potential and formation of apoptotic bodies and autophagic vesicles were observed in HKUST-1-treated HEK293 cells. Oxidative (oxidative stress and haem oxygenase-1 activation) and inflammatory responses (NF-κB and NLRP3 activation) in HEK293 cells were induced by HKUST-1 exposure. In addition, the observed reduction in NAD(P)H levels in HKUST-1-treated HEK293 cells may be attributable to PARP-1 activation following DNA single- and double-strand breaks. The HKUST-1-induced depletion of zonula occludens proteins in HEK293 cells might lead to altered renal barrier integrity. The variations of α1-antitrypsin, oxidised α1-antitrypsin and NLRP3 protein expression in HEK293 cells suggested that HKUST-1 increases the risk of chronic kidney diseases. However, most of these adverse effects were significantly induced only by high HKUST-1 concentration (100 μg/mL), which do not reflect the actual exposure. Thus, the toxic risk of HKUST-1 appears to be negligible.
目前，人们对HKUST-1的研究涉及非常广泛的应用领域。尽管HKUST-1具有令人兴奋的潜力，但人们对其安全性仍存在重大担忧。因此，使用人胚肾293（HEK293）细胞来验证HKUST-1的肾毒性。在本研究中，HKUST-1在HEK293细胞中诱导了浓度依赖性的细胞毒性作用。在经HKUST-1处理的HEK293细胞中观察到线粒体膜电位的去极化以及凋亡小体和自噬小泡的形成。HKUST-1暴露诱导了HEK293细胞中的氧化（氧化应激和血红素加氧酶-1激活）和炎症反应（NF-κB和NLRP3激活）。此外，在经HKUST-1处理的HEK293细胞中观察到的NAD(P)H水平降低可能归因于DNA单链和双链断裂后PARP-1的激活。HKUST-1诱导的HEK293细胞中紧密连接蛋白的消耗可能导致肾屏障完整性改变。HEK293细胞中α1-抗胰蛋白酶、氧化型α1-抗胰蛋白酶和NLRP3蛋白表达的变化表明HKUST-1增加了慢性肾脏病的风险。然而，这些不良反应大多仅在高浓度HKUST-1（100μg/mL）下显著诱导，这并不能反映实际暴露情况。因此，HKUST-1的毒性风险似乎可以忽略不计。
