Silver Nanoparticles Induced Oxidative Stress and Mitochondrial Injuries Mediated Autophagy in HC11 Cells Through Akt/AMPK/mTOR Pathway
Abstract
Silver nanoparticles (AgNPs) are widely used in industrial products, and they have good antibacterial properties, with potential for prevention and treatment of cow mastitis. However, concerns exist about the cytotoxicity of AgNPs. Thus, we have studied the role of autophagy in AgNP-induced cytotoxicity in mouse HC11 mammary epithelium cells. We found that AgNPs injured HC11 cells, with release of lactate dehydrogenase (LDH). AgNPs also induced autophagy in HC11 cells, which was associated with oxidative stress, as indicated by increased reactive oxygen species (ROS) and increased expression of hemoxygenase-1(HO-1) and Nrf2. Mitochondria were altered by AgNPs: mitochondrial membrane potential (MMP) was decreased and the expression of PINK1 and Parkin was increased. AgNPs also increased the expression of p-AMPK and decreased the expression of p-Akt and p-mTOR. The addition of 3-methyl adenine inhibited autophagy and enhanced the cytotoxicity of AgNPs, indicating that autophagy is protective against AgNP-induced cell death. In summary, AgNPs induced protective autophagy in HC11 cells via the Akt/AMPK/mTOR pathway, associated with cellular oxidative stress and mitochondrial alterations. Our research confirms that AgNPs may damage the breast tissue in clinical applications and should be used with caution. Further research is necessary to clarify whether the damage caused by AgNPs will affect the lactation function of the mammary glands and possible residues in milk.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Silver nanoparticles cause significant neurotoxicity at concentrations above 10 μg/ml in primary cortical neurons, resulting in increased production of reactive oxygen species and lactate dehydrogenase release.
“For example, silver nanoparticles (AgNPs) have been reported to cause significant neurotoxicity at concentrations above 10 μg/ml in primary cortical neurons, resulting in increased production of ROS and lactate dehydrogenase (LDH) release [179].”
From Targeted Nanoparticles for Drug Delivery Across the Blood–Brain Barrier in Early and Late Stages of Alzheimer's Disease: A Review (2026) · cites this paper as [179]
Metallic nanoparticles such as silver, gold, or iron oxide cause dose- and time-dependent cytotoxicity in neural systems, primarily due to oxidative stress, mitochondrial damage, and pro-inflammatory responses.
“Metallic NPs, such as those made of silver, gold, or iron oxide, have been shown to cause dose- and time-dependent cytotoxicity in neural systems, primarily due to oxidative stress, mitochondrial damage, and pro-inflammatory responses.”
From Targeted Nanoparticles for Drug Delivery Across the Blood–Brain Barrier in Early and Late Stages of Alzheimer's Disease: A Review (2026) · cites this paper as [179]
Cites
Ivankovic, D., Chau, K., Schapira, A. H. V., & Gegg, M. E. (2016) · Journal of Neurochemistry · doi:10.1111/jnc.13412 · Cited by 264 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Kochman, U., Sitka, H., Kuźniar, J., Czaja, M., Kozubek, P., Beszłej, J. A., & Leszek, J. (2026) · Molecular Neurobiology · doi:10.1007/s12035-025-05417-z · Cited by 60 · see citing works
- Authors
- Hou, J., Zhao, L., Tang, H., He, X., Ye, G., Shi, F., Kang, M., Chen, H., & Li, Y.
- Affiliations
- Sichuan Agricultural University (CN)
- Corresponding author
- Li, Yinglun
- Venue
- Biological Trace Element Research
- Published
- 2020-07-14
- Volume
- 199
- Issue
- 3
- Pages
- 1062-1073
- ISSN
- 0163-4984 (ISSN-L)
- 1559-0720
- OpenAlex
- W3042585535
- Cited by
- 45
- References
- 1
- Citations by year
- 2026: 6 · 2025: 4 · 2024: 8 · 2023: 8 · 2022: 10 · 2021: 7 · 2020: 2
- FWCI
- 2.63
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biological Trace Element Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Physical Sciences › Materials Science › Materials Chemistry › Nanoparticles: synthesis and applications
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Physical Sciences › Engineering › Biomedical Engineering › Graphene and Nanomaterials Applications
- Keywords
- silver nanoparticles, nanoparticle cytotoxicity, autophagy, oxidative stress, mitochondrial damage, reactive oxygen species, heme oxygenase-1, Nrf2, PINK1, Parkin, mitochondrial membrane potential, 3-methyladenine
- MeSH terms
- Animals, Autophagy, Female, Mitochondria, Silver, Reactive Oxygen Species, Oxidative Stress, Proto-Oncogene Proteins c-akt, Mice, Metal Nanoparticles, AMP-Activated Protein Kinases, TOR Serine-Threonine Kinases
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
