Gold Nanoparticles Induce Oxidative Stress and Apoptosis in Human Kidney Cells
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, AuNP...
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| Format: | Article |
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MDPI AG
2020-05-01
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| Series: | Nanomaterials |
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| Online Access: | https://www.mdpi.com/2079-4991/10/5/995 |
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| author | Maria Enea Eulália Pereira Miguel Peixoto de Almeida Ana Margarida Araújo Maria de Lourdes Bastos Helena Carmo |
| author_facet | Maria Enea Eulália Pereira Miguel Peixoto de Almeida Ana Margarida Araújo Maria de Lourdes Bastos Helena Carmo |
| author_sort | Maria Enea |
| collection | DOAJ |
| description | 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 (Δ<i>Ψ</i>m), 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 (<i>p</i> ≤ 0.01). For the MUA-coated 13 nm nanospheres, these effects were associated also to increased levels of total glutathione (<i>p</i> ≤ 0.01) and enhanced ATP production (<i>p</i> ≤ 0.05). Programmed cell death was detected through the activation of both extrinsic and intrinsic pathways (caspase 8 and 9) (<i>p ≤</i> 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. |
| first_indexed | 2024-03-10T19:39:46Z |
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| institution | Directory Open Access Journal |
| issn | 2079-4991 |
| language | English |
| last_indexed | 2024-03-10T19:39:46Z |
| publishDate | 2020-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Nanomaterials |
| spelling | doaj.art-76465cfbbb464285af03bda0d338d88a2023-11-20T01:22:28ZengMDPI AGNanomaterials2079-49912020-05-0110599510.3390/nano10050995Gold Nanoparticles Induce Oxidative Stress and Apoptosis in Human Kidney CellsMaria Enea0Eulália Pereira1Miguel Peixoto de Almeida2Ana Margarida Araújo3Maria de Lourdes Bastos4Helena Carmo5UCIBIO/REQUIMTE, Laboratório de Toxicologia, Departamento de Ciências Biológicas, Faculdade de Farmácia, Universidade do Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, PortugalLAQV/REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, Rua Campo Alegre, 687, 4169-007 Porto, PortugalLAQV/REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, Rua Campo Alegre, 687, 4169-007 Porto, PortugalUCIBIO/REQUIMTE, Laboratório de Toxicologia, Departamento de Ciências Biológicas, Faculdade de Farmácia, Universidade do Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, PortugalUCIBIO/REQUIMTE, Laboratório de Toxicologia, Departamento de Ciências Biológicas, Faculdade de Farmácia, Universidade do Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, PortugalUCIBIO/REQUIMTE, Laboratório de Toxicologia, Departamento de Ciências Biológicas, Faculdade de Farmácia, Universidade do Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, PortugalGold 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 (Δ<i>Ψ</i>m), 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 (<i>p</i> ≤ 0.01). For the MUA-coated 13 nm nanospheres, these effects were associated also to increased levels of total glutathione (<i>p</i> ≤ 0.01) and enhanced ATP production (<i>p</i> ≤ 0.05). Programmed cell death was detected through the activation of both extrinsic and intrinsic pathways (caspase 8 and 9) (<i>p ≤</i> 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.https://www.mdpi.com/2079-4991/10/5/995gold nanoparticles (AuNPs)HK-2 cellsnanospheresnanostarssizecapping |
| spellingShingle | Maria Enea Eulália Pereira Miguel Peixoto de Almeida Ana Margarida Araújo Maria de Lourdes Bastos Helena Carmo Gold Nanoparticles Induce Oxidative Stress and Apoptosis in Human Kidney Cells Nanomaterials gold nanoparticles (AuNPs) HK-2 cells nanospheres nanostars size capping |
| title | Gold Nanoparticles Induce Oxidative Stress and Apoptosis in Human Kidney Cells |
| title_full | Gold Nanoparticles Induce Oxidative Stress and Apoptosis in Human Kidney Cells |
| title_fullStr | Gold Nanoparticles Induce Oxidative Stress and Apoptosis in Human Kidney Cells |
| title_full_unstemmed | Gold Nanoparticles Induce Oxidative Stress and Apoptosis in Human Kidney Cells |
| title_short | Gold Nanoparticles Induce Oxidative Stress and Apoptosis in Human Kidney Cells |
| title_sort | gold nanoparticles induce oxidative stress and apoptosis in human kidney cells |
| topic | gold nanoparticles (AuNPs) HK-2 cells nanospheres nanostars size capping |
| url | https://www.mdpi.com/2079-4991/10/5/995 |
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