p53, MAPKAPK-2 and caspases regulate nickel oxide nanoparticles induce cell death and cytogenetic anomalies in rats

The unique properties of nickel oxide nanoparticles (NiO-NPs) distinguish it from traditional nickel containing materials, and enable its industrial application as an advanced nanomaterial. Despite the benefits, the in vivo toxicological studies on NiO-NPs have been mainly focused on its pulmonary pathology. However, NiO-NPs exposure via oral route and its subsequent toxic effects in exposed animals are still lacking. Hence, we evaluated the NiO-NPs oral toxicity in male Wistar rats. NiO-NPs induced significant increase in chromosomal aberrations (CAs), micronuclei (MN) formation and, DNA damage in rats. Flow cytometric analysis showed apoptosis, ROS generation and dysfunction of mitochondrial membrane potential (ΔΨm). Imbalance of antioxidant enzymes, along with histological alterations was found in liver. Taking together, these results unequivocally suggested that NiO-NPs induced toxicity was through cyto-genetic alterations, oxidative stress, apoptosis and liver toxicity. The western blotting data validated the interplay of p53 and MAPKAPK-2 signalling via activation of caspases 8, 3, cyto c, pro-apoptotic bax and anti-apoptotic bcl-2 proteins.