Copper Oxide Nanoparticle-Induced Acute Inflammatory Response and Injury in Murine Lung Is Ameliorated by Synthetic Secoisolariciresinol Diglucoside (LGM2605)

Abstract

Metal-oxide nanoparticles (MO-NPs), such as the highly bioreactive copper-based nanoparticles (CuO-NPs), are widely used in manufacturing of hundreds of commercial products. Epidemiological studies correlated levels of nanoparticles in ambient air with a significant increase in lung disease. CuO-NPs, specifically, were among the most potent in a set of metal-oxides and carbons studied in parallel regarding DNA damage and cytotoxicity. Despite advances in nanotoxicology research and the characterization of their toxicity, the exact mechanism(s) of toxicity are yet to be defined. We identified chlorination toxicity as a damaging consequence of inflammation and myeloperoxidase (MPO) activation, resulting in macromolecular damage and cell damage/death. We hypothesized that the inhalation of CuO-NPs elicits an inflammatory response resulting in chlorination damage in cells and lung tissues. We further tested the protective action of LGM2605, a synthetic small molecule with known scavenging properties for reactive oxygen species (ROS), but most importantly, for active chlorine species (ACS) and an inhibitor of MPO. CuO-NPs (15 µg/bolus) were instilled intranasally in mice and the kinetics of the inflammatory response in lungs was evaluated 1, 3, and 7 days later. Evaluation of the protective action of LGM2605 was performed at 24 h post-challenge, which was selected as the peak acute inflammatory response to CuO-NP. LGM2605 was given daily via gavage to mice starting 2 days prior to the time of the insult (100 mg/kg). CuO-NPs induced a significant inflammatory influx, inflammasome-relevant cytokine release, and chlorination damage in mouse lungs, which was mitigated by the action of LGM2605. Preventive action of LGM2605 ameliorated the adverse effects of CuO-NP in lung.

Differences in the characteristics and pulmonary toxicity of nano- and micron-sized respirable coal dust

“…lung injury [28,29]. Characterization analysis of CD in this study indicated that CD-NPs may have higher toxicity due to lower oxygen-to-carbon ratio, smaller size, and larger surface area.…”

“…In addition, small particles have a larger surface area. Smaller particles with larger surface area have high capacity to play a key role in nanoparticle-induced lung injury [ 28 , 29 ]. Characterization analysis of CD in this study indicated that CD-NPs may have higher toxicity due to lower oxygen-to-carbon ratio, smaller size, and larger surface area.…”

Non-ROS-Mediated Cytotoxicity of ZnO and CuO in ML-1 and CA77 Thyroid Cancer Cell Lines

“…Pcd1l2g is another inflammatory gene upregulated in CA77 cells after treatment ( Figure 11 ). It is clear that CuO MONPs cause increased inflammation as reported many times in the recent literature [ 41 , 42 , 43 ]. Given that CuO MONPs can bind to cell death ligands to induce non-ROS-mediated apoptosis [ 44 ], our RNAseq studies further confirm non-ROS-mediated apoptosis through increased inflammation pathways.…”

Comparative toxicological evaluations of novel forms nano-pesticides in liver and lung of albino rats

“…These in accordance with Rabia et al (2019) who suggested that CuONPs displayed histological changes which correlated with the recorded increased in liver AST and ALT. According to Pietrofesa et al (2021) inhalation of CuO NPs causes an inflammatory reaction that damages cells and lung tissues. In the current microscopic observations, the liver of CuONSp treated rats showed proliferation of bile ductules, newly developed bile ductules surrounded by mononuclear leukocytic infiltration at the end of experiment.…”