Metallothionein, an endogenous antioxidant protein, protects against acute lung injury caused by air pollutants.

Reducing deaths and diseases due to air pollution is a global challenge enshrined in the Sustainable Development Goals. Currently, there is an urgent need to discover factors that protect the lungs and bronchi, which are the first to be injured and undergo oxidative stress when air pollutants enter the body, and to establish methods to prevent their onset and progression. Metallothionein, a protein present in humans that exerts detoxification and antioxidant effects on toxic metals, has long been known to exert protective effects against liver and kidney diseases. However, no functional analysis of the effects of metallothionein on acute lung injury caused by air pollutants has been reported. Thus, we studied the effect of metallothionein on urban aerosol-dependent acute lung injury using metallothionein knockout (MT-KO) mice and a metallothionein inducer. Most importantly, we found that urban aerosol-dependent acute lung injury was exacerbated in MT-KO mice compared to wild-type (WT) mice. In addition, inflammatory responses and reactive oxygen species production in the lungs were enhanced in MT-KO mice compared to WT mice. Furthermore, we found that the intraperitoneal administration of zinc acetate exerted an antioxidant effect via the induction of metallothionein providing a protective effect against the development of urban aerosol-dependent acute lung injury. These results suggest that the metallothionein protein itself or compounds with metallothionein-inducing action may help prevent acute lung injury caused by air pollutants.