Identification of potential biomarkers of gold nanoparticle toxicity in rat brains.
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 amino-butyric 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.


CONCLUSIONS
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.
Department of Biochemistry, College of Science, King Saud University, PO Box 22452, Riyadh 11495, Saudi Arabia. nikhat@ksu.edu.sa
Nikhat J
NJ
Siddiqi
Mohamed Anwar K
MA
Abdelhalim
Afaf K
AK
El-Ansary
Abdullah S
AS
Alhomida
W Y
WY
Ong
D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000502:physiology; D015415:Biomarkers / Q000737:chemistry; D001923:Brain Chemistry / Q000187:drug effects* / Q000502:physiology; D000075202:Contraindications; D005979:Glutathione Peroxidase / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000172:deficiency; D006046:Gold / Q000737:chemistry / Q000633:toxicity*; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D008297:Male; D053768:Metal Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar
D000975:Antioxidants; D015415:Biomarkers; D006046:Gold; D005979:Glutathione Peroxidase