Reduced graphene oxide mitigates cadmium-induced cytotoxicity and oxidative stress in HepG2 cells

Numerous applications of reduced graphene oxide (RGO) and pervasive cadmium (Cd) have led concern about their co-exposure to the environment and human. We studied the combined effects of RGO and Cd in human liver (HepG2) cells. Initially, we found that RGO (up to 50 μg/ml) did not harm to HepG2 cells while Cd induced dose-dependent (1-10 μg/ml) cytotoxicity. Exciting observations were that a non-cytotoxic concentration of RGO (25 μg/ml) effectively mitigates the toxic effects of Cd (2 μg/ml) such as cell viability reduction, lactate dehydrogenase release, and irregular cell morphology. Cd-induced cell cycle arrest, induction of caspases (3 and 9) enzymes activity, and loss of mitochondrial membrane potential were also significantly alleviated by RGO co-exposure. Moreover, generation of pro-oxidants (reactive oxygen species and hydrogen peroxide levels) and depletion of antioxidants (glutathione level and superoxide dismutase activity) due to Cd exposure was effectively attenuated by RGO co-exposure. Mitigating effect of RGO could be due to strong adsorption of Cd on the large surface area of RGO sheets, which decrease the cellular uptake and bioavailability of Cd for HepG2 cells. This study warrants future research on potential mechanisms of mitigating effects of RGO against Cd-induced toxicity in animal models.