Sub-Acute Toxicity Study of Graphene Oxide in the Sprague-Dawley Rat

Li, Yingbo; Wang, Yan; Tu, Liu; Chen, Di; Luo, Zhi; Liu, Dengyuan; Miao, Zhuang; Feng, Gang; Li, Qing; Wang, Shali

doi:10.3390/ijerph13111149

Cited by 35 publications

(27 citation statements)

References 37 publications

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“…The present results are in agreement with the study of Li et al 31 showing that the injection of GO into male Sprague Dawley rats caused no significant changes in the…”

supporting

confidence: 94%

In vivo toxicological evaluation of graphene oxide nanoplatelets for clinical application

Amrollahi-Sharifabadi

Koohi

Zayerzadeh³

et al. 2018

IJN

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BackgroundGraphene is considered as a wonder material; it is the strongest material on the planet, super-elastic, and conductive. Its application in biomedicine is huge, with a multibillion-dollar industry, and will revolutionize the diagnostic and treatment of diseases. However, its safety and potential toxicity is the main challenge.MethodsThis study assessed the potential toxicity of graphene oxide nanoplatelets (GONs) in an in vivo animal model using systemic, hematological, biochemical, and histopathological examinations. Normal saline (control group) or GONs (3–6 layers, lateral dimension=5–10 μm, and thickness=0.8–2 nm) at dose rate of 50, 150, or 500 mg/kg were intraperitoneally injected into adult male Wistar rats (n=5) every 48 hours during 1 week to receive each animal a total of four doses. The animals were allowed 2 weeks to recover after the last dosing. Then, animals were killed and the blood was collected for hematological and biochemical analysis. The organs including the liver, kidney, spleen, lung, intestine, brain, and heart were harvested for histopathological evaluations.ResultsThe results showed GONs prevented body weight gain in animals after 21 days, treated at 500 mg/kg, but not in the animals treated at 150 or 50 mg/kg GONs. The biochemical analysis showed a significant increase in total bilirubin, with a significant decrease in triglycerides and high-density lipoprotein in animals treated at 500 mg/kg. Nonetheless, other hematological and biochemical parameters remained statistically insignificant in all GONs treated animals. The most common histopathological findings in the visceral organs were granulomatous reaction with giant cell formation and accumulation of GONs in capsular regions. Also, small foci of neuronal degeneration and necrosis were the most outstanding findings in the brain, including the cerebellum.ConclusionIn conclusion, this study shows that GONs without functionalization are toxic. The future study is a comparison of the functionalized with non-functionalized GONs.

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“…The present results are in agreement with the study of Li et al 31 showing that the injection of GO into male Sprague Dawley rats caused no significant changes in the…”

supporting

confidence: 94%

In vivo toxicological evaluation of graphene oxide nanoplatelets for clinical application

Amrollahi-Sharifabadi

Koohi

Zayerzadeh³

et al. 2018

IJN

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“…The main drawback of conventional chemotherapy is the adverse effects on the body as it cannot deliver selective action specifically to the cancer cells, thus damaging the surrounding normal healthy cells or rapidly dividing healthy cells such as the cells of gastrointestinal tract, bone marrow, hair follicles, causing issues like cardiac, hepatic, pulmonary, renal and gastrointestinal toxicities [ 4 , 5 , 6 ]. Drug delivery systems offer numerous advantages over tradition chemotherapy such as targeted delivery at disease site, sustained release leading to prolonged bioavailability, lower dosage requirement and improved drug solubility among others [ 7 , 8 , 9 , 10 , 11 , 12 ]. Significant impact has been made by the application of nanotechnology in medicine for theranostic agents development which can diagnose and cure the diseases simultaneously [ 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

Improved Anticancer Effect of Magnetite Nanocomposite Formulation of GALLIC Acid (Fe3O4-PEG-GA) Against Lung, Breast and Colon Cancer Cells

et al. 2018

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Lung cancer, breast cancer and colorectal cancer are the most prevalent fatal types of cancers globally. Gallic acid (3,4,5-trihydroxybenzoic acid) is a bioactive compound found in plants and foods, such as white tea, witch hazel and it has been reported to possess anticancer, antioxidant and anti-inflammatory properties. In this study we have redesigned our previously reported anticancer nanocomposite formulation with improved drug loading based on iron oxide magnetite nanoparticles coated with polyethylene glycol and loaded with anticancer drug gallic acid (Fe3O4-PEG-GA). The in vitro release profile and percentage drug loading were found to be better than our previously reported formulation. The anticancer activity of pure gallic acid (GA), empty carrier (Fe3O4-PEG) nanocarrier and of anticancer nanocomposite (Fe3O4-PEG-GA) were screened against human lung cancer cells (A549), human breast cancer cells (MCF-7), human colon cancer cells (HT-29) and normal fibroblast cells (3T3) after incubation of 24, 48 and 72 h using (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) MTT assay. The designed formulation (Fe3O4-PEG-GA) showed better anticancer activity than free gallic acid (GA). The results of the in vitro studies are highly encouraging to conduct the in vivo studies.

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“…Moreover, in open field tests and functional observational battery tests, graphene oxide injections into rat tail veins for 7 days at concentrations of 2.5, 5, and 10 mg/kg body weight did not produce behavioral changes, yet caused inflammation of the lungs, liver, and spleen at a high concentration (10 mg/kg). The graphene oxide injections also reduced the cholesterol, high density lipoprotein (HDL), and low-density lipoprotein levels (Li et al, 2016). Another graphene oxide acute inhalation toxicity study also showed that acute inhalation exposure to graphene oxide induced minimal toxic responses in the lungs of male Sprague-Dawley rats at concentrations of 0.46 and 3.76 mg/m 3 without increasing the inflammatory markers (Han et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Short-term inhalation study of graphene oxide nanoplates

Kim

et al. 2018

Nanotoxicology

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Graphene oxides possess unique physicochemical properties with important potential applications in electronics, pharmaceuticals, and medicine. However, the toxicity following inhalation exposure to graphene oxide has not yet been clarified. Therefore, this study conducted a short-term graphene oxide inhalation toxicity analysis using a nose-only inhalation exposure system and male Sprague-Dawley rats. A total of four groups (15 rats per group) were exposed: (1) control (fresh air), (2) low concentration (0.76 ± 0.16 mg/m), (3) moderate concentration (2.60 ± 0.19 mg/m), and (4) high concentration (9.78 ± 0.29 mg/m). The rats were exposed to graphene oxide for 6 h/day for 5 days, followed by recovery for 1, 3, and 21 days. No significant body or organ weight changes were noted after the short-term exposure or during the recovery period. Similarly, no significant systemic effects of toxicological importance were noted in the hematological assays, bronchoalveolar lavage fluid (BAL) inflammatory markers, BAL fluid cytokines, or blood biochemical assays following the graphene oxide exposure or during the post-exposure observation period. Moreover, no significant differences were observed in the BAL cell differentials, such as lymphocytes, macrophages, or polymorphonuclear cells. Graphene oxide-ingested alveolar macrophages as a spontaneous clearance reaction were observed in the lungs of all the concentration groups from post 1 day to post 21 days. Histopathological examination of the liver and kidneys did not reveal any significant test-article-relevant histopathological lesions. Importantly, similar to previously reported graphene inhalation data, this short-term nose-only inhalation study found only minimal or unnoticeable graphene oxide toxicity in the lungs and other organs.

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Sub-Acute Toxicity Study of Graphene Oxide in the Sprague-Dawley Rat

Cited by 35 publications

References 37 publications

In vivo toxicological evaluation of graphene oxide nanoplatelets for clinical application

In vivo toxicological evaluation of graphene oxide nanoplatelets for clinical application

Improved Anticancer Effect of Magnetite Nanocomposite Formulation of GALLIC Acid (Fe3O4-PEG-GA) Against Lung, Breast and Colon Cancer Cells

Short-term inhalation study of graphene oxide nanoplates

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