In vitro renal toxicity evaluation of copper-based metaleorganic framework HKUST-1 on human embryonic kidney cells

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 etreated HEK293 cells. Oxidative (oxidative stress and haem oxygenase-1 activation) and inflammatory responses (NF-kappa B 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-1einduced depletion of zonula occludens proteins in HEK293 cells might lead to altered renal barrier integrity. The variations of a1-antitrypsin, oxidised alpha 1-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 mg/mL), which do not reflect the actual exposure. Thus, the toxic risk of HKUST-1 appears to be negligible. (C) 2021 Elsevier Ltd. All rights reserved.

Automated summary

HKUST-1 induced concentration-dependent cytotoxic effects in HEK293 cells, causing depolarization of mitochondrial membrane potential, formation of apoptotic bodies and autophagic vesicles, as well as oxidative and inflammatory responses. HKUST-1 may lead to reduced NAD(P)H levels and depletion of zonula occludens proteins, increasing the risk of chronic kidney diseases. However, most adverse effects were significantly induced only at high concentrations, suggesting the toxic risk of actual exposure to HKUST-1 can be negligible.