Silver-doped graphene oxide nanocomposite triggers cytotoxicity and apoptosis in human hepatic normal and carcinoma cells

Daoud Ali, Saud Alarifi, Saad Alkahtani, Rafa S Almeer Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia Introduction: Graphene oxide nanoparticles have been widely used in industry and biomedical fields due to their unique physicochemical properties. However, comparative cytotoxicity of silver-doped reduced graphene oxide (rGO–Ag) nanoparticles on normal and cancerous liver cells has not been well studied yet. Materials and methods: This study aimed at determining the toxic potential of rGO–Ag nanocomposite on human liver normal (CHANG) and cancer (HepG2) cells. The rGO–Ag nanocomposite was characterized by using different advanced instruments, namely, dynamic light scattering, scanning electron microscope, and transmission electron microscope. Results: The rGO–Ag nanocomposite reduced cell viability and impaired cell membrane integrity of CHANG and HepG2 cells in a dose-dependent manner. Additionally, it induced reactive oxygen species generation and reduced mitochondrial membrane potential in both cells in a dose-dependent manner. Moreover, the activity of oxidative enzymes such as lipid peroxide, superoxide dismutase, and catalase were increased and glutathione was reduced in both cells exposed to rGO–Ag nanocomposite. Pretreatment with N-acetylcysteine inhibited cytotoxicity and reactive oxygen species generation in CHANG and HepG2 cells exposed to rGO–Ag nanocomposite (50 µg/mL). DNA damage was determined by Comet assay and maximum DNA damage occurred at rGO–Ag nanocomposite (25 µg/mL) for 24 h. It is also valuable to inform that HepG2 cells appear to be slightly more susceptible to rGO–Ag nanocomposite exposure than CHANG cells. Conclusion: This result provides a basic comparative toxic effect of rGO–Ag nanocomposite on hepatic normal and cancerous liver cells. Keywords: oxidative stress, CHANG and HepG2 cells, cytotoxicity, DNA fragmentation, apoptosi