Abstract
Copper oxide nanoparticles (CuONPs) are one of the widely used metal nanoparticles in the industrial and commercial fields. Autophagy is an intracellular degradation system that delivers cytoplasmic constituents to the lysosome and has been linked to nanoparticles-induced toxicity. In particular, the roles of autophagy in response to CuONPs have been explored in vitro, although the conclusions are controversial. To clarify the role of autophagy in CuONPs-induced acute lung injury, microtubule-associated protein 1 light chain 3 beta (Map1lc3b or lc3b) knockout mice and their corresponding wild type mice are applied. Our results showed that single-dose intratracheal instillation of CuONPs with dosages of 1.25, 2.5 or 5 mg/kg caused acute lung injury 3 days after treatment in a dose-dependent manner, as evidenced by deteriorative lung histopathology, more infiltration of macrophage cells, increased oxidative stress and copper ions. Loss of lc3b resulted in aggravated lung injury induced by CuONPs, which was probably due to the blockade of mitophagy and consequently the accumulation of aberrant mitochondria with overloaded copper ions. Our study provides the first in vivo evidence that autophagy deficiency exacerbates CuONPs-induced acute lung injury, and highlights that targeting autophagy is a meaningful strategy against CuONPs-associated respiratory toxicity.
Highlights
Owing to the excellent photovoltaic and photoconductive properties, copper oxide nanoparticles (CuONPs) have attracted great attentions and have been widely used in industrial and commercial fields such as energy storage, electrochemistry, antifouling coatings, catalysis, sensors/ biosensors and biocidal agents [1]
This study provides the first in vivo evidence indicating that loss of autophagic key factor lc3b results in more severe acute lung injury upon CuONPs treatment, which was probably due to the blockade of mitophagy and the accumulation of aberrant mitochondria with overloaded copper ions
Characteristic of copper oxide nanoparticles (CuONPs) The size and morphology of the CuONPs were characterized by transmission electron microscopy (TEM)
Summary
Owing to the excellent photovoltaic and photoconductive properties, copper oxide nanoparticles (CuONPs) have attracted great attentions and have been widely used in industrial and commercial fields such as energy storage, electrochemistry, antifouling coatings, catalysis, sensors/ biosensors and biocidal agents [1]. The increasing production and application of CuONPs have drawn attention to the potential harmful effects on human health. Compared with SiO2, TiO2, Fe2O3 and Fe3O4 nanoparticles, CuONPs exhibit the greatest toxicity dose-dependently in many cell models [5]. The toxic effects that follow include: cytotoxic, genotoxic, and oxidative stress responses, which have been reported by our group [7,8,9] and other groups [3, 10]. Our previous studies demonstrated that chelation of copper ions can significantly reverse cell death induced by CuONPs [7, 9], suggesting the crucial role of copper ions in CuONPs-induced cytotoxicity
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