Usefulness of myeloperoxidase as a biomarker for nanoparticles' toxicity

Abstract

Myeloperoxidase (MPO) synthesized in neutrophils is involved in the lung injury, and it has been suggested MPO is involved in inflammation and fibrosis of the lung via the oxidative stress. To investigate MPO as a biomarker for pulmonary toxicities of nanoparticles, we performed an intratracheal instillation study of nanoparticles and measured the concentration of MPO. Nickel oxide nanoparticles (NiO) and two titanium dioxide nanoparticles (TiO₂) (Rutile, P90) were used as chemicals with high and low toxicities, respectively. 0.2 mg or 1.0 mg of NiO or two TiO₂ were intratracheally instilled in male rats (about 12 weeks old). MPO in the bronchoalveolar lavage fluid (BALF) were determined using an ELISA kit at 3 days, 1week and 1 month after end of exposure.

Dispersed NiO induced significantly increase of MPO concentration in BALF from 3 days to 1 month, compared with negative control groups. On the other hand, dispersed two TiO₂ induced significantly increase of MPO concentration in BALF at 3 days, however the tendency of decrease of MPO concentration was observed in two TiO₂ exposure groups, and the level was almost the same as in the negative controls. We observed that nanoparticles with high toxicities induced the tendency of persistent increase of MPO concentration, and nanoparticles with low toxicities induced transient increase of MPO concentration. Taken together, it is suggested that MPO is useful as a biomarker for nanoparticles' toxicity.

This work is partially supported by “Development of innovative methodology for safety assessment of industrial nanomaterials" by Ministry of Economy, Trade and Industry (METI) of Japan.