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Neurotoxicity of silver nanoparticles in the animal brain: a systematic review and meta-analysis

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Abstract

Objective

About 30% of all nanoparticle products contain silver nanoparticles (AgNPs). With the increasing use of AgNPs in industry and medicine, concerns about the adverse effects on the environment, and the possible toxicity of these particles to primary cells and towards organs such as the brain and nervous system increased. In this paper, the toxicity of AgNPs in neurons and brain of animal models was investigated by a systematic review and meta-analysis.

Methods

The full texts of 26 relevant studies were reviewed and analyzed. Data from nine separate experiments in five articles were analyzed by calculating the standardized mean differences between viability of treated animals and untreated groups. Subgroup analysis was conducted. In addition, a systematic review provided a complete, exhaustive summary of all articles.

Results

The results of the meta-analysis showed that AgNPs are able to cause neuronal death after entering the brain (standardized mean difference (SMD) = 2.87; 95% confidence interval (CI) 2.1–3.61; p < 0.001). AgNPs sized smaller or larger than 10 nm could both cause neuronal cell death. This effect could be observed for a long time (up to 6 months). Neurons from embryonic animals whose mothers had been exposed to AgNPs during pregnancy were affected as much as animals that were themselves exposed to AgNPs. Toxic effects of AgNPs on memory and cognitive function were also observed. Studies have shown that inflammation and increased oxidative stress followed by apoptosis are likely to be the main mechanisms of AgNPs toxicity.

Conclusion

AgNPs can enter the brain with a long half-life and it can cause neuronal death after entering the brain. AgNPs can manifest proinflammatory cascades in the CNS and BBB. Some toxic effects were detected in the cerebral cortex, hypothalamus, hippocampus and others. Studies have shown that inflammation and increased oxidative stress lead to apoptosis, the main mechanism of AgNPs neurotoxicity, which can be caused by an increase in silver ions from AgNPs.

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Availability of data and materials

The data that support the findings of this study are available from the corresponding author (FR) on request.

Code availability

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Funding

FR was supported by [IRAN University of Medical Sciences], Grants Number [98-3-32-16261]. MRH was supported by [US NIH] Grant] numbers [R01AI050875] and [R21AI121700].

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Author notes

  1. Atousa Janzadeh and Zahra Behroozi are co-first authors.

Authors and Affiliations

  1. Radiation Biology Research Center, Iran University of Medical Sciences, Tehran, Iran

    Atousa Janzadeh

  2. Department of Physiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

    Zahra Behroozi

  3. Department of Medical Nanotechnology, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran

    Farzaneh saliminia

  4. Occupational Medicine Research Center (OMRC), Iran University of Medical Sciences (IUMS), Tehran, Iran

    Narges Janzadeh

  5. Department of Medical Physics and Biomedical Engineering, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Hossein Arzani

  6. Research Center of Advanced Technologies in Medicine, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, Iran

    Hossein Arzani

  7. Department of Biostatistics, School of Public Health, Iran University of Medical Sciences, Tehran, Iran

    Kiarash Tanha

  8. Laser Research Centre, Faculty of Health Science, University of Johannesburg, Doornfontein, 2028, South Africa

    Michael R. Hamblin

  9. Physiology Research Center, Iran University of Medical Sciences, Tehran, Iran

    Fatemeh Ramezani

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  1. Atousa Janzadeh
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Correspondence to Michael R. Hamblin or Fatemeh Ramezani.

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Janzadeh, A., Behroozi, Z., saliminia, F. et al. Neurotoxicity of silver nanoparticles in the animal brain: a systematic review and meta-analysis. Forensic Toxicol 40, 49–63 (2022). https://doi.org/10.1007/s11419-021-00589-4

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