Sublethal exposure of small few-layer graphene promotes metabolic alterations in human skin cells

Small few-layer graphene (sFLG), a novel small-sized graphene-related material (GRM), can be considered as an intermediate degradation product of graphene. GRMs have a promising present and future in the field of biomedicine. However, safety issues must be carefully addressed to facilitate their implementation. In the work described here, the effect of sub-lethal doses of sFLG on the biology of human HaCaT keratinocytes was examined. A one-week treatment of HaCaTs with sub-lethal doses of sFLG resulted in metabolome remodeling, dampening of the mitochondrial function and a shift in the redox state to pro-oxidant conditions. sFLG raises reactive oxygen species and calcium from 24 h to one week after the treatment and this involves the activation of NADPH oxidase 1. Likewise, sFLG seems to induce a shift from oxidative phosphorylation to glycolysis and promotes the use of glutamine as an alternative source of energy. When sub-toxic sFLG exposure was sustained for 30 days, an increase in cell proliferation and mitochondrial damage were observed. Further research is required to unveil the safety of GRMs and degradation-derived products before their use in the workplace and in practical applications.