Investigation of Gene Expression of MMP-2 and TIMP-2 mRNA in Rat Lung in Inhaled Nickel Oxide and Titanium Dioxide Nanoparticles

Abstract

In order to investigate whether or not dispersed nanoparticles have an effect of inflammation and fibrosis on animals, we developed a nanoparticle generation system and examined the gene expression of matrix metalloproteinase (MMP) and tissue inhibitor matrix proteinase (TIMP) in rat lung containing inhaled nickel oxide (NiO) or titanium dioxide (TiO₂) nanoparticles. In both experiments, Wistar male rats were exposed to NiO or TiO₂ nanoparticles for 4 wk (6 h/day). The geometric mean diameters of NiO and TiO₂ in the chamber were 139 ± 12 nm and 51 ± 9 nm, respectively. The average concentration of the particle number of NiO and TiO₂ was 1.0E+05 /cm³ and 2.8E+05 /cm³, respectively. At 4 d, 1 and 3 months after the end of the inhalation, the rats exposed to these particles were sacrificed and the gene expressions of MMP-2, TIMP-2 and type I collagen were measured using RT-PCR. Pathological finding revealed that there was minimum inflammation with nickel oxide only at 4 d and no change with titanium oxide. However, there were no changes of the gene expression of MMP-2, TIMP-2, and type I collagen in either the NiO or TiO₂ exposure groups. In this study, inhalation of nickel oxide and titanium dioxide nanoparticles did not induce the gene expression of MMP-2 and TIMP-2 mRNA in rat lungs.