Metabolomics approach to study in vivo toxicity of graphene oxide nanosheets

Abstract

Although graphene oxide (GO) nanosheets are widely used in different fields, the mechanism of their toxicity remains relatively unknown. NMR‐based metabolomics was used to study in vivo time and dose‐dependent toxicity of GO nanosheets in mice. Sixty serum samples from mice in four different time intervals including 24 and 72 h and 7 and 21 days after injection of 0‐, 1‐, and 10‐mg/kg b.w. were analyzed based on 1HNMR spectra of each sample and multivariate methods. In comparison with the control group, 12 changed metabolites were identified in GO nanosheet‐treated mice groups. These metabolites are involved in steroid hormone biosynthesis and steroid biosynthesis pathways. It was seen that the time factor is more important than the dose factor and the groups were separated in a time direction, completely. We found that GO nanosheets has toxicity and can affect steroidal hormones. However, this study shows that after 21 days, the treated groups regardless of their GO nanosheet dose are very close to the control group. This means that in one step exposure to GO nanosheets, their toxicity diminished after 21 days.

Synthesis and Functionalization of Graphene Materials for Biomedical Applications: Recent Advances, Challenges, and Perspectives

“…The adsorption of steroid hormones on GO nanosheets is a good example, where hydrophobic and electrostatic interactions present in long‐range up to 10 nm and short ranges (2–5 nm) interactions include π – π stacking, van der Waals forces, and hydrogen bonding. [ 134 ] Several groups adapted self‐assembly to connect DNA, [ 131 ] SS‐GrBP5 mutant, [ 10 ] polyoxyethylene sorbitan laurate (TWEEN 20), [ 126 ] and photoreceptor proteins [ 17 ] to graphene.…”

“…Researchers aim to develop a method that overcomes the limitations of the lack of organ donors, disease transmission, and immune reactions using regenerated tissue produced with biocompatible scaffolds. [ 116–175 ] Materials used for tissue engineering need to be biocompatible as well as without inducing immune reactions (not toxic). Graphene materials can be applied as substrates due to their unique electrical and mechanical properties.…”

“…[137,145] Generally, ROS generation is caused by two pathways in mammal cell lines, including 1) a defence mechanism against foreign substances by macrophages, [1] 2) lipid peroxidation in the mitochondrial respiratory chain and polyunsaturated mitochondrial membrane. [134] Generation of ROS in macrophages follows route (1), where ROS generation is part of a defence mechanism against foreign substances by macrophages as well as a marker for its activation, [1] and the increase of ROS level activates signaling of various routes, finally induce cytokine secretion and cell apoptosis. [111a] p-G was reported to activate mitogen-activated protein kinase and transform growth factor-𝛽 (TGF-𝛽) signaling, activating two proapoptotic members, Bim and Bax, of the Bcl-2 protein family.…”

Emerging metallenes: synthesis strategies, biological effects and biomedical applications

“…The in vivo toxic effects of 2D biomaterials have been systematically studied, such as graphene and black phosphorus. 133,134 However, systematical research on the in vivo toxicity of metallenes is rarely carried out. Based on the present research, more attention should be paid to the in vivo toxicity of metallenes for promoting their biomedical applications.…”

Trends and prospects in graphene and its derivatives toxicity research: A bibliometric analysis

“…The toxicity of graphene and its derivatives in cells depends on several factors, including the exposure dose, exposure time, and physicochemical properties of graphene and its derivatives. In vivo animal toxicity tests have shown that the main routes of exposure to graphene and its derivatives include oral administration (Yu et al, 2019), inhalation, and injection (Ghiasvand Mohammadkhani et al, 2022; Ruiz et al, 2020). After oral and nasal inhalation or intratracheal, intravenous, or peritoneal administration, graphene and its derivatives can be further transferred through the circulatory system across the blood–brain barrier and tend to accumulate in the liver, lungs, kidneys, and brain, inducing granulomas in the liver, kidneys, lungs, and spleen of mice (Devasena et al, 2021).…”