Engineered Nanomaterial Impact in the Liver following Exposure via an Intravenous Route–The Role of Polymorphonuclear Leukocytes and Gene Expression in the Organ

Background and methods: Following exposure via a number of routes (inhalation, ingestion or injection), someNanomaterials (NMs) translocate to secondary tissues, prominently the liver. This study investigated the effects of anarray of NMs, varying in their physicochemical characteristics, consisting of two types of Zinc Oxide (ZnO), two MultiwalledCarbon Nanotubes (MWCNT), one silver (Ag) and one titanium dioxide (TiO2) on the liver, following Intravenous(IV) exposure of C57/BL6 mice. The animals were exposed to either a single dose of NM (128 μg/ml–100 μl) or threedoses of (64 μg/ml–100 μl), every 24 hr. Animals were dissected 6, 24, 48 and 72 hr after the single IV injection, or 72hr after the triple injection regime.Results and conclusions: A Myeloperoxidase (MPO) assay was utilised to quantify neutrophil influx into thetissue. However, as MPO is also found in other granulocytes in smaller quantities, the neutrophils in the liver tissue werealso labelled, using a specific neutrophil cell surface marker (Ly-6B.2). A wide array of NMs (including ZnO, Ag, TiO2and MWCNT) induced a neutrophil influx into the liver, as early as 6 hr post IV exposure. However, the neutrophils wereonly involved in the initial phases of the immune response against the NMs, as the leukocyte numbers had returned tocontrol levels after 48 hr. Finally, analysis of mRNA expression in mice livers showed alterations in levels of C3, IL6,IL10, CXCL2 and ICAM-1