Investigating the role of catalase mimetic cerium oxide-based nanozyme to impart protection to hepatic cells from acatalasia

Cellular catalase enzyme imparts protection to cells from the deleterious effects of reactive oxygen species (ROS) produced mainly due to the decomposition of hydrogen peroxide into water and molecular oxygen. Lowered level of cellular catalase enzyme can induce several human diseases such as acatalasemia, type 2 diabetes mellitus, and vitiligo. Recent development of nanomaterials exhibiting biological enzyme like activities (nanozymes) have shown tremendous potential as biomedicines. Among them, cerium oxide nanoparticles (CeNPs) have emerged as an effective therapeutic nanozyme due to their redox-based ability to interchange the +IV or +III oxidation states from the surface “Ce” atoms. CeNPs containing high Ce +IV oxidation state in their surface “Ce” atoms are shown to exhibit hydrogen peroxide degradation activity, similar to catalase enzyme. In this study, we have investigated the ability of CeNPs to protect normal human liver cells (WRL-68) exposed with 3-Amino-1,2,4-Triazole (3-AT), which is an irreversible inhibitor of catalase enzyme. Our results revealed that CeNPs protect cells from the cytotoxic as well as genotoxic effects aroused due to the nonfunctional cellular catalase enzyme. Uptake results suggest that CeNPs are actively internalized in WRL-68 cells and scavenge the free radicals generated due to elevated levels of hydrogen peroxide inside the cells. Additionally, we also observed that CeNPs can protect hepatic cells from undergone early apoptosis than late apoptosis. Interestingly, CeNPs did not alter the natural antioxidant defense system of cells even in the absence of functional catalase enzyme, which suggest that the observed protection was probably due to the hydrogen peroxide degradation by CeNPs. The results of this study substantiate the reinforcement of CeNPs as pharmacological agents for the treatment of human diseases related to nonfunctional biological enzymes.