Metabolomics approach to study in vivo toxicity of graphene oxide nanosheets

• Published in: Journal of applied toxicology 2022-03, Vol.42 (3), p.506-515
• Main Authors: Ghiasvand Mohammadkhani, Leila, Khoshkam, Maryam, Kompany‐Zareh, Mohsen, Amiri, Mahdi, Ramazani, Ali
• Format: Article
• Language: English
• Subjects: 1HNMR; Animals; Biocompatibility; Biosynthesis; Graphene; graphene oxide; Graphite - toxicity; Hormones; In vivo methods and tests; Male; Metabolites; Metabolomics; Metabolomics - instrumentation; Mice; Nanosheets; Nanostructures - toxicity; nanotoxicometabolomics; NMR; Nuclear magnetic resonance; PLSDA; Random Allocation; steroid hormone biosynthesis; Steroids; Time factors; Toxicity; Toxicity Tests
• ISSN: 0260-437X; 1099-1263
• DOI: 10.1002/jat.4235

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. 1H nuclear magnetic resonance (1HNMR) method and chemometric method were used to analyze the metabolites of serum samples to discover the in vivo toxicological mechanisms of graphene oxide (GO) nanosheets in mice. Maximum toxicity of GO nanosheet‐treated groups compared with control group was in 72 h and 7 days. Samples were not dose dependent but only time dependent. Steroid hormone biosynthesis and steroid biosynthesis were the most affected pathways by GO nanosheets.