Nanodiamond-induced increase in ROS and RNS levels activates NF-κB and augments thiol pools in human hepatocytes

• Nanodiamonds (NDs, 10 μg/ml) did not provoke hepatocyte cell death.
• NDs induced oxidative and nitrosative stress.
• NDs activated redox-sensitive NF-κB pathway.
• NDs promoted NF-κB-mediated and thiol-based adaptive response in human hepatocytes.

Nanodiamonds (NDs) are considered non-toxic and nanodiamond-based materials are widely used in nanotechnology and nanomedicine. However, little is known about their biological effects at low concentrations not causing cytotoxicity, especially that nanodiamonds may affect not only primary organs directly exposed but also secondary organs, such as the liver, spleen, kidneys, heart and brain, upon systemic distribution. In the present study, we used human hepatocytes to evaluate hepatocyte response to ND low concentration treatment. 10 μg/ml NDs did not provoke cytotoxic effects in a hepatocyte cell. In contrast, NDs caused the imbalance of intracellular redox equilibrium. NDs induced an increase in the levels of total reactive oxygen species (ROS), mitochondrial superoxide and nitric oxide. NDs also activated redox state-sensitive NF-κB pathway promoting cell survival and modulating the levels of reduced glutathione (GSH). ND-mediated increase in p65 nuclear signals and a concomitant augmentation in thiol pools may be a part of adaptive response after nanodiamond treatment in a hepatocyte cell.