Immunotoxic potential of nanoparticles of cerium oxide and gadolinium oxide in human monocyte (THP-1) cells

Abstract

ObjectivesNPs of cerium oxide (CeO2) and gadolinium oxide (Gd2O3; designated as GO for simplicity) belong to the lanthanide group of elements. Due to the potential applications of GO NPs in MRI or CeO2 NPs as novel antioxidant, attention about their impact on the immune-toxicity is needed. MethodsPotential immune-toxicity response due to interactions of GO NPs (54.8 ± 29 nm in length and 13.7 ± 6 nm in diameter with a fiber-like shape) and CeO2 NPs (40 ± 17 nm with a cuboidal shape) was examined in human monocytic THP-1 cells exposed for 24 h, 48 h and 72 h. A battery of parameters intended to measure oxidative stress and mechanism of cell death, if occurring, in THP-1 cells exposed to NPs for the periods as mentioned above was also examined. ResultsNPs of GO induced higher toxicity and oxidative stress than it was by NPs of CeO2. Interestingly, CeO2 NPs behaved as antioxidant when exposed for 24 h at concentrations of 100- and 200 µg/mL. This trend, however, reversed at 72 h of exposure that resulted in induction of significant cytotoxicity, reactive oxygen species (ROS) and exhaustion of cellular antioxidant glutathione (GSH). Cuboid CeO2 NPs with low potential to induce toxicity and oxidative stress caused a rise in Bax/Bcl2 ratio and caspase 3 apoptotic markers in THP-1 cells. Lack of these apoptotic markers in more toxic fiber-like GO NPs treated THP-1 cells indicate an apoptosis-independent mechanism of cell death by GO NPs. Although, CeO2 NPs caused induction of interleukin-1β (IL-1β) after 72 of exposure, CeO2 NPs did not induce tumor necrosis factor-α (TNF-α) at any duration of exposure. ConclusionDespite belonging to same rare-earth metal groups in lanthanide series, NPs of GO and CeO2 induce different bio-responses in human immune THP-1 cells. GO NPs were highly inflammatory than the NPs of CeO2. To the best of our knowledge, this is the first report on comparative analysis carried out for these NP’s potential cytotoxicity, oxidative stress and inflammation in THP-1 cells.