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Open AccessArticle

Gold Nanoparticles Induce Oxidative Stress and Apoptosis in Human Kidney Cells

1
UCIBIO/REQUIMTE, Laboratório de Toxicologia, Departamento de Ciências Biológicas, Faculdade de Farmácia, Universidade do Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal
2
LAQV/REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, Rua Campo Alegre, 687, 4169-007 Porto, Portugal
*
Authors to whom correspondence should be addressed.
Nanomaterials 2020, 10(5), 995; https://doi.org/10.3390/nano10050995
Received: 17 April 2020 / Revised: 14 May 2020 / Accepted: 16 May 2020 / Published: 22 May 2020
(This article belongs to the Special Issue Safety and Biocompatibility of Metallic Nanoparticles)
Gold nanoparticles (AuNPs) are highly attractive for biomedical applications. Therefore, several in vitro and in vivo studies have addressed their safety evaluation. Nevertheless, there is a lack of knowledge regarding their potential detrimental effect on human kidney. To evaluate this effect, AuNPs with different sizes (13 nm and 60 nm), shapes (spheres and stars), and coated with 11-mercaptoundecanoic acid (MUA) or with sodium citrate, were synthesized, characterized, and their toxicological effects evaluated 24 h after incubation with a proximal tubular cell line derived from normal human kidney (HK-2). After exposure, viability was assessed by the MTT assay. Changes in lysosomal integrity, mitochondrial membrane potential (ΔΨm), reactive species (ROS/RNS), intracellular glutathione (total GSH), and ATP were also evaluated. Apoptosis was investigated through the evaluation of the activity of caspases 3, 8 and 9. Overall, the tested AuNPs targeted mainly the mitochondria in a concentration-dependent manner. The lysosomal integrity was also affected but to a lower extent. The smaller 13 nm nanospheres (both citrate- and MUA-coated) proved to be the most toxic among all types of AuNPs, increasing ROS production and decreasing mitochondrial membrane potential (p ≤ 0.01). For the MUA-coated 13 nm nanospheres, these effects were associated also to increased levels of total glutathione (p ≤ 0.01) and enhanced ATP production (p ≤ 0.05). Programmed cell death was detected through the activation of both extrinsic and intrinsic pathways (caspase 8 and 9) (p ≤ 0.05). We found that the larger 60 nm AuNPs, both nanospheres and nanostars, are apparently less toxic than their smaller counter parts. Considering the results herein presented, it should be taken into consideration that even if renal clearance of the AuNPs is desirable, since it would prevent accumulation and detrimental effects in other organs, a possible intracellular accumulation of AuNPs in kidneys can induce cell damage and later compromise kidney function. View Full-Text
Keywords: gold nanoparticles (AuNPs); HK-2 cells; nanospheres; nanostars; size; capping gold nanoparticles (AuNPs); HK-2 cells; nanospheres; nanostars; size; capping
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MDPI and ACS Style

Enea, M.; Pereira, E.; Peixoto de Almeida, M.; Araújo, A.M.; Bastos, M.L.; Carmo, H. Gold Nanoparticles Induce Oxidative Stress and Apoptosis in Human Kidney Cells. Nanomaterials 2020, 10, 995.

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