What Are the Side Effects of Graphene Oxide in Humans?

Graphene oxide (GO) is a two-dimensional carbon compound, an oxidized form of graphene, composed of single or few layers of carbon atoms. It has oxygen-containing functional groups attached to its carbon plane and edges, which distinguish its properties from graphene itself. These functional groups allow GO to disperse easily in water and other polar solvents. GO is a nanomaterial, often produced from graphite through oxidation processes like the modified Hummers method.

Understanding Graphene Oxide’s Journey in the Body

Graphene oxide can enter the human body through several potential routes, including inhalation, ingestion, and direct skin contact. Once inside the body, GO can be distributed to various organs.

Studies indicate that GO tends to accumulate in organs such as the lungs, liver, spleen, and kidneys. For instance, inhaled GO particles can deposit in the respiratory tract and move into the lower airways. The body’s ability to eliminate GO depends on factors like its form and particle size, with smaller particles potentially being more easily absorbed and distributed.

How Graphene Oxide Interacts with Cells

Graphene oxide interacts with cells and tissues through several mechanisms. One such mechanism is cellular uptake, where GO particles are internalized by cells. The size and surface properties of GO influence how it enters cells; for example, larger protein-coated GO nanoparticles (around 1 micrometer) may enter through phagocytosis, while smaller ones (around 500 nanometers) might use clathrin-mediated endocytosis.

Upon entering biological fluids, GO encounters proteins that can bind to its surface, forming a “protein corona.” This protein layer can alter GO’s properties and how it interacts with cells, potentially reducing its uptake and mitigating its toxicity. The composition and amount of this protein corona can significantly influence the cellular response and overall toxicity.

Graphene oxide also has the potential to induce oxidative stress by generating reactive oxygen species (ROS) within cells. Excessive ROS production can damage cellular components like proteins, DNA, and lipids, and disrupt normal cellular signaling pathways. This oxidative stress can lead to inflammation, as GO’s exposed surface may cause more lipid peroxidation and contribute to higher cellular toxicity.

Additionally, GO can cause physical damage to cell membranes. It may adhere to, wrap around, or even insert into the lipid bilayer of cell membranes. This disruption can increase membrane permeability, potentially allowing more ROS to enter the cell and intensify internal oxidative stress.

Potential Adverse Effects on Human Health

Exposure to graphene oxide can lead to various adverse effects on human health, primarily observed in animal and in vitro human cell studies. The respiratory system is particularly susceptible to GO exposure through inhalation. This can result in lung inflammation, the formation of granulomas, and pulmonary fibrosis, which is the scarring of lung tissue.

The cardiovascular system can also be affected by graphene oxide. Research suggests potential impacts on blood clotting and the integrity of blood vessels. Severe reactions, including anaphylactic death, have been observed in some animal studies.

Graphene oxide may also modulate the immune system, potentially altering normal immune responses. Furthermore, there is concern about neurological effects, as some graphene-family nanoparticles can penetrate the blood-brain barrier. The possibility of neurotoxicity remains an area of investigation.

Regarding genotoxicity, GO has the potential to cause DNA damage, which can be a precursor to various cellular dysfunctions including apoptosis or unregulated cell growth. Studies have shown that GO exposure can lead to increased lactate dehydrogenase (LDH) leakage, a marker of cell damage, and decreased mitochondrial membrane potential, indicating impaired cellular energy production.

Other organs, such as the liver and kidneys, may also experience toxicity. For example, some studies involving intravenous injection of GO nanoflakes in rats showed accumulation primarily in the liver within 24 hours, alongside elevated serum parameters indicating liver and kidney stress. These findings emphasize that GO can interfere with the normal physiological functions of organs, with the severity of effects often depending on the dose and specific properties of the GO.

Current Research Insights and Safety Considerations

Research into graphene oxide’s safety profile is ongoing and complex, with numerous factors influencing its potential toxicity. Factors such as the material’s size, shape, surface chemistry, functionalization, dose, and route of exposure all play a role in determining its biological impact. For instance, smaller GO particles may be more readily absorbed, while larger particles might cause more significant mechanical damage to cells.

Challenges in accurately assessing long-term human health impacts persist due to the relatively new nature of the material and the varied forms it can take. There is a recognized need for standardized testing methods and clearer regulatory guidelines to ensure consistent safety evaluations. Continued research is necessary to fully understand the long-term effects and to facilitate the safe integration of GO technologies into various applications.

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