Graphene oxide-induced, reactive oxygen species-mediated mitochondrial dysfunctions and apoptosis: high-dose toxicity in normal cells

Nanomedicine (Lond). 2023 May;18(11):875-887. doi: 10.2217/nnm-2023-0129. Epub 2023 Jul 20.

Abstract

Aim: The cytotoxic effects of graphene oxide nanoparticles (GONPs) using MTT assays, observance of apoptotic markers, and oxidative stress were outlined. Materials & methods: Rat embryonic fibroblasts (REFs) and human epithelial breast cells (HBLs) were used at 250, 500 and 750 μg/ml concentrations. Results: Significant cytotoxic and apoptotic effects were observed. Analyses of CYP2E1 and malondialdehyde concentrations in REF and HBL-100 cell lines after exposing to GONPs confirmed the nanomaterials toxicity. However, the glutathione levels in REF and HBL-100 cell lines showed a substantial reduction compared with the control. The cytochrome CYP2E1, glutathione, malondialdehyde and caspase-3 alterations provided a plausible interlinked relationship. Conclusion: The study confirmed the GONPs cytotoxic effects on REF and HBL-100 cell lines. The outcome suggested caution in wide-spread applications of GONPs, which could have implications for occupational health also.

Keywords: GONPs; ROS; apoptosis; cytotoxicity; free radicals; graphene oxide; high-dose vulnerability; nanomaterials; nanoparticles; nanotoxicity; oxidative damage; oxidative stress; toxicity.

MeSH terms

  • Animals
  • Antineoplastic Agents* / pharmacology
  • Apoptosis
  • Cell Survival
  • Cytochrome P-450 CYP2E1* / metabolism
  • Cytochrome P-450 CYP2E1* / pharmacology
  • Glutathione / metabolism
  • Humans
  • Malondialdehyde / metabolism
  • Mitochondria / metabolism
  • Oxidative Stress
  • Rats
  • Reactive Oxygen Species / metabolism

Substances

  • Reactive Oxygen Species
  • graphene oxide
  • Cytochrome P-450 CYP2E1
  • Antineoplastic Agents
  • Glutathione
  • Malondialdehyde