The short- and long-term effects of orally administered high-dose reduced graphene oxide nanosheets on mouse behaviors

Zhang, Ding; Zhang, Zheyu; Liu, Yayun; Chu, Maoquan; Yang, Chengyu; Li, Wenhao; Shao, Yuxiang; Yan, Yue; Xu, Rujiao

doi:10.1016/j.biomaterials.2015.07.060

Cited by 66 publications

(43 citation statements)

References 65 publications

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“…Graphene nanosheets exposure was also observed to impair vital behaviors, including locomotion, learning and memory, and deemed to damage neuronal systems (Yang et al, ). However, in a recent report, reduced graphene oxide (r‐GO) nanosheets showed little change in exploratory, anxiety‐like, or learning and memory behaviors, although general locomotor activity, balance and neuromuscular coordination were initially affected in mice (Zhang et al, ). A series of studies have suggested that nanomaterials elicit toxicity to C. elegans (Wang, ; Yang et al, ; Zhao et al, ).…”

Section: Discussionmentioning

confidence: 99%

Chronic exposure to graphene-based nanomaterials induces behavioral deficits and neural damage inCaenorhabditis elegans

et al. 2017

J. Appl. Toxicol.

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Nanomaterials of graphene and its derivatives have been widely applied in recent years, but whose impacts on the environment and health are still not well understood. In the present study, the potential adverse effects of graphite (G), graphite oxide nanoplatelets (GO) and graphene quantum dots (GQDs) on the motor nervous system were investigated using nematode Caenorhabditis elegans as the assay system. After being characterized using TEM, SEM, XPS and PLE, three nanomaterials were chronically exposed to C. elegans for 6 days. In total, 50-100 mg l GO caused a significant reduction in the survival rate, but G and GDDs showed low lethality on nematodes. After chronic exposure of sub-lethal dosages, three nanomaterials were observed to distribute primarily in the pharynx and intestine; but GQDs were widespread in nematode body. Three graphene-based nanomaterials resulted in significant declines in locomotor frequency of body bending, head thrashing and pharynx pumping. In addition, mean speed, bending angle-frequency and wavelength of the crawling movement were significantly reduced after exposure. Using transgenic nematodes, we found high concentrations of graphene-based nanomaterials induced down-expression of dat-1::GFP and eat-4::GFP, but no significant changes in unc-47::GFP. This indicates that graphene-based nanomaterials can lead to damages in the dopaminergic and glutamatergic neurons. The present data suggest that chronic exposure of graphene-based nanomaterials may cause neurotoxicity risks of inducing behavioral deficits and neural damage. These findings provide useful information to understand the toxicity and safe application of graphene-based nanomaterials. Copyright © 2017 John Wiley & Sons, Ltd.

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Section: Discussionmentioning

confidence: 99%

Chronic exposure to graphene-based nanomaterials induces behavioral deficits and neural damage inCaenorhabditis elegans

et al. 2017

J. Appl. Toxicol.

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“…To evaluate the functions of spatial learning and memory, the rats (n=8 per group) were assessed by MWM test, as described previously 35. Briefly, the test was performed in a round, flat-bottomed black plastic pool (Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking, People’s Republic of China) with a diameter of 150 cm and a height of 50 cm.…”

Section: Methodsmentioning

confidence: 99%

Dexmedetomidine attenuates the propofol-induced long-term neurotoxicity in the developing brain of rats by enhancing the PI3K/Akt signaling pathway

Xiao

Zhou

et al. 2018

NDT

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BackgroundPropofol induces short- and long-term neurotoxicity. Our previous study showed that dexmedetomidine (Dex) can attenuate the propofol-induced acute neurotoxicity in rodents by enhancing the PI3K/Akt signaling. However, whether treatment of young rats with Dex could protect them from long-term neurotoxicity induced by propofol is unclear.Materials and methodsSeven-day-old male Sprague Dawley rats were randomized and injected intraperitoneally with saline (100 μL, NS), propofol (100 mg/kg), Dex (75 μg/kg), propofol (100 mg/kg) plus Dex (25, 50 or 75 μg/kg), 10% dimethyl sulfoxide (DMSO, 100 μL) or TDZD-8 (a GSK3β inhibitor, 1 mg/kg), or intracerebroventricularly with DMSO (5 μL) or LY294002 (a PI3K inhibitor, 25 μg/5 μL DMSO). Other rats in the experimental group were injected with the same doses of propofol, Dex and LY294002 or TDZD-8. All the rats were monitored until they were 9 weeks old. Their spatial learning and memory were tested by Morris water maze. The neuronal apoptosis, expression of PSD95, expression and phosphorylation of Akt and GSK3β and synaptic ultrastructures were determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, immunohistochemistry, Western blot and transmission electron microscopy assays, respectively.ResultsCompared with the NS control group, young rats injected with intralipid, Dex, TDZD-8, LY294002 or DMSO alone did not show any significant change as they aged. Propofol significantly increased the escape latency time, hippocampal neuroapoptosis and synaptic ultrastructural changes but decreased the relative levels of PSD95 expression, and Akt and GSK3β phosphorylation in the developing hippocampus of the rats. The neuronal toxic effects of propofol were significantly mitigated by the pretreatment with a higher dose of Dex. The neuroprotective effect of Dex was enhanced by the treatment with TDZD-8, but was completely abrogated by the treatment with LY294002.ConclusionOur results indicated that the pretreatment of young rats with Dex attenuated the propofol-induced long-term neurotoxicity in their developing hippocampus by enhancing the PI3K/Akt signaling.

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“…al. have investigated the short-term and long-term effects of reduced GO (rGO) on general locomotor activity, neuromuscular coordination, balance, anxiety, learning and memory of male C57b/6 mice (6–8 weeks old) using rotarod, open field and Morris water maze tests [111]. HEPES Buffer dispersed rGO were administered via oral gavage every 24 hours for 5 days at 60mg/kg dose.…”

Section: In Vivo Toxicologymentioning

confidence: 99%

Toxicology of graphene-based nanomaterials

Lalwani

D’Agati

Khan

et al. 2016

Advanced Drug Delivery Reviews

248

151

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Graphene based nanomaterials possess remarkable physiochemical properties suitable for diverse applications in electronics, telecommunications, energy and healthcare. The human and environmental exposure to graphene-based nanomaterials is increasing due to advancements in the synthesis, characterization and large-scale production of graphene and the subsequent development of graphene based biomedical and consumer products. A large number of in vitro and in vivo toxicological studies have evaluated the interactions of graphene-based nanomaterials with various living systems such as microbes, mammalian cells, and animal models. A significant number of studies have examined the short- and long-term in vivo toxicity and biodistribution of graphene synthesized by variety of methods and starting materials. A key focus of these examinations is to properly associate the biological responses with chemical and morphological properties of graphene. Several studies also report the environmental and genotoxicity response of pristine and functionalized graphene. This review summarizes these in vitro and in vivo studies and critically examines the methodologies used to perform these evaluations. Our overarching goal is to provide a comprehensive overview of the complex interplay of biological responses of graphene as a function of their physio-chemical properties.

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The short- and long-term effects of orally administered high-dose reduced graphene oxide nanosheets on mouse behaviors

Cited by 66 publications

References 65 publications

Chronic exposure to graphene-based nanomaterials induces behavioral deficits and neural damage inCaenorhabditis elegans

Chronic exposure to graphene-based nanomaterials induces behavioral deficits and neural damage inCaenorhabditis elegans

Dexmedetomidine attenuates the propofol-induced long-term neurotoxicity in the developing brain of rats by enhancing the PI3K/Akt signaling pathway

Toxicology of graphene-based nanomaterials

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