ナノマテリアルと粒子の肺毒性

抄録

Hazard assessment for manufactured nanomaterials: Along with the development of nanotechnology, variety of nanomaterials have been designed and manufactured. However, the hazard of nanomaterials has not been studied fully. Inhalation study is considered a golden standard for hazard assessment of nanomaterials, but alternative method of intratracheal instillation is usually used in academia because of the limitation of facilities.

Safe by design: To develop safer nanomaterials, knowledge how the design of nanomaterials can reduce the hazard of nanomaterials is needed. We compared bare silica nanoparticles and amino or carboxyl-functionalized silica nanoparticles for pulmonary toxicity in mice. The study shows amino- or carboxyl-functionalization of silica nanoparticles reduces the inflammation in lung and toxicity to macrophage, thus providing useful information for development of safer nanomaterials.

Role of Nrf2 in pulmonary effect of manufactured nanomaterials: Nrf2 is known to be a master regulator for anti-oxidative-stress genes. However, recent studies showed Nrf2 negatively regulate expression of proinflammatory cytokines. We compared pulmonary effect of exposure to zinc oxide nanoparticles between Nrf2 null mice and wild type mice. The result shows that deletion of Nrf2 enhances inflammatory response for exposure to zinc oxide nanoparticles in the lung of mice, suggesting inhibitory effect of Nrf2 on zinc oxide-induced pulmonary inflammation.

Systemic effect of particles: Recent epidemiological studies show association between air pollution and cognitive dysfunction. One of hazardous compositions of particulate matter is polycyclyic aromatic hydrocarbons such as benzopyrene. An epidemiological study also suggests neurobehavioral effect of benzopyrene on workers. We are studying neurobehavioral and neurotoxicological effect of benzopyrene in mice by pharyngeal aspiration method, and the result shows harmful effect of benzopyrene on the density of noradrenergic axons and behavior.

Conclusions: Information on effect of particles, not only nanoparticles but also conventional or unintentionally produced particles in humans suggests us the priority of research on manufacture nanomaterials. Not only pulmonary toxicity but also systemic effect of nanomaterials or particles should be studied further.