Identification of potential biomarkers of gold nanoparticle toxicity in rat brains
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RESEARCH
JOURNAL OF NEUROINFLAMMATION
Open Access
Identification of potential biomarkers of gold nanoparticle toxicity in rat brains Nikhat J Siddiqi1*, Mohamed Anwar K Abdelhalim2, Afaf K El-Ansary1, Abdullah S Alhomida1 and W Y Ong3,4
Abstract Background: Gold nanoparticles (AuNPs) are finding increased use in therapeutics and imaging. However, their toxic effects still remain to be elucidated. Therefore this study was undertaken to study the biochemical effects of AuNPs on rat brain and identify potential biomarkers of AuNP toxicity. Methods: Male Wister rats weighing 150–200 g were injected with 20 μg/kg body weight of 20-nm gold nanoparticles for 3 days through the intraperitoneal route. The rats were killed by carbon dioxide asphyxiation 24 h after the last dose of gold nanoparticle injection. The parameters studied included lipid peroxidation, glutathione peroxidase, 8- hydroxydeoxyguanosine, caspase-3, heat shock protein70, serotonin, dopamine, gamma aminobutyric acid and interferon-γ. Results: In this study AuNPs caused generation of oxidative stress and a decrease of antioxidant enzyme, viz., glutathione peroxidase activity in rat brain. This was accompanied by an increase in 8-hydroxydeoxyguanosine, caspase-3 and heat shock protein70, which might lead to DNA damage and cell death. Gold nanoparticles also caused a significant decrease in the levels of neurotransmitters like dopamine and serotonin, indicating a possible change in the behavior of the treated animals. There was a significant increase in the cerebral levels of IFN-γ in treated animals. Conclusion: This study concludes that AuNPs cause generation of oxidative stress and an impairment of the antioxidant enzyme glutathione peroxidase in rat brain. AuNPs also cause generation of 8-hydroxydeoxyguanosine (8OHdG), caspase-3 and heat shock protein70 (Hsp70), and IFN-γ, which may lead to inflammation and DNA damage/cell death. Keywords: Gold nanoparticles, Oxidative stress, Antioxidant enzyme, DNA damage, Cell death, Interferon-γ, Neurotransmitters
Background The emerging field of nanobiotechnology offers the potential for the development of exquisitely sensitive diagnostics and organ/tumor-targeted therapies [1]. Over the past few decades, there has been considerable interest in developing nanoparticles as effective drug delivery devices [1]. Gold nanoparticles (AuNPs) are expected to have a wide range of applications in the future because they are easy to synthesize and have good biocompatibility. Studies of Sonavan et al. 2008 [1] have demonstrated a wide distribution of gold particles inside the * Correspondence: [email protected] 1 Department of Biochemistry, College of Science, King Saud University, P.O. Box 22452, Riyadh 11495, Saudi Arabia Full list of author information is available at the end of the article
living system. Their studies have shown that 15–50-nm AuNPs can cross the blood–brain barrier, resulting in their accumulation in the brain [1]. The biosafety of metallic gold in well known, and it has been in in vivo use since the
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