Graphene Oxide and Reduced Graphene Oxide Exhibit Cardiotoxicity Through the Regulation of Lipid Peroxidation, Oxidative Stress, and Mitochondrial Dysfunction

Abstract

ObjectiveGraphene has been widely used for various biological and biomedical applications due to its unique physiochemical properties. This study aimed to evaluate the cardiotoxicity of graphene oxide (GO) and reduced GO (rGO) in vitro and in vivo, as well as to investigate the underlying toxicity mechanisms.MethodsGO was reduced by gamma irradiation to prepare rGO and then characterized by UV/visible light absorption spectroscopy. Rat myocardial cells (H9C2) were exposed to GO or rGO with different absorbed radiation doses. The in vitro cytotoxicity was evaluated by MTT assay, cell apoptosis assay, and lactate dehydrogenase (LDH) activity assay. The effects of GO and rGO on oxidative damage and mitochondrial membrane potential were also explored in H9C2 cells. For in vivo experiments, mice were injected with GO or rGO. The histopathological changes of heart tissues, as well as myocardial enzyme activity and lipid peroxidation indicators in heart tissues were further investigated.ResultsrGO was developed from GO following different doses of gamma irradiation. In vitro experiments in H9C2 cells showed that compared with control cells, both GO and rGO treatment inhibited cell viability, promoted cell apoptosis, and elevated the LDH release. With the increasing radiation absorbed dose, the cytotoxicity of rGO gradually increased. Notably, GO or rGO treatment increased the content of ROS and reduced the mitochondrial membrane potential in H9C2 cells. In vivo experiments also revealed that GO or rGO treatment damaged the myocardial tissues and changed the activities of several myocardial enzymes and the lipid peroxidation indicators in the myocardial tissues.ConclusionGO exhibited a lower cardiotoxicity than rGO due to the structure difference, and the cardiotoxicity of GO and rGO might be mediated by lipid peroxidation, oxidative stress, and mitochondrial dysfunction.

Graphene Oxide and Reduced Graphene Oxide Nanoflakes Coated with Glycol Chitosan, Propylene Glycol Alginate, and Polydopamine: Characterization and Cytotoxicity in Human Chondrocytes

“…A study on H9C2 rat myocardial cells showed an increasing level of LDH while testing higher concentrations for rGO with respect to GO. It is relevant to declare that the average size of GO and rGO was in the order of 200 nm [ 58 ]. In another study, a better performance was shown by rGO with respect to GO when dealing with the same size (0.4–0.8 µm).…”

The Preliminary Study on the Proapoptotic Effect of Reduced Graphene Oxide in Breast Cancer Cell Lines

“…It is interesting that the other form of graphene can affect cell receptors and disrupt metabolism by inhibiting glucose or amino acid supply, which leads to the induction of endoplasmic reticulum (ER) stress, apoptosis or autophagy. Moreover, graphene itself can bind intracellular nutrients from the cell culture medium, which limits their availability and inhibits cellular proliferation and viability [4,5].…”

“…Graphene (G) and its derivatives, referred to as nanomaterials from the graphene family (GFNs), include graphene oxide (GO), its reduced form (rGO), single-or few-layer graphene, graphene nanosheets (GNS), and graphene nanoribbons [4,5]. However, the most important chemical derivative of graphene is GO.…”

Comparison of the Toxicity of Pristine Graphene and Graphene Oxide, Using Four Biological Models

“…Mittali et al [ 47 ] also noted that unoxidized, thermally reduced GO induces higher viability reduction in comparison to GO. Some studies show that the gradually increasing total ROS content was exhibited in cells with GO or rGO treatment [ 48 ]. However, Gurunathan et al [ 43 ] presented that the level of ROS production was significantly higher in rGO-treated cells than in GO-treated cells.…”