Pulmonary Toxicity and Proteomic Analysis in Bronchoalveolar Lavage Fluids and Lungs of Rats Exposed to Copper Oxide Nanoparticles

Abstract

Copper oxide nanoparticles (CuO NPs) were intratracheally instilled into lungs at concentrations of 0, 0.15, and 1.5 mg/kg bodyweight to 7-week-old Sprague–Dawley rats. The cytotoxicity, immunotoxicity, and oxidative stress were evaluated, followed by proteomic analysis of bronchoalveolar lavage fluid (BALF) and lungs of rats. The CuO NPs-exposed groups revealed dose-dependent increases in total cells, polymorphonuclear leukocytes, lactate dyhydrogenase, and total protein levels in BALF. Inflammatory cytokines, including macrophage inflammatory protein-2 and tumor necrosis factor-α, were increased in the CuO NPs-treated groups. The expression levels of catalase, glutathione peroxidase-1, and peroxiredoxin-2 were downregulated, whereas that of superoxide dismutase-2 was upregulated in the CuO NPs-exposed groups. Five heat shock proteins were downregulated in rats exposed to high concentrations of CuO NPs. In proteomic analysis, 17 proteins were upregulated or downregulated, and 6 proteins were validated via Western blot analysis. Significant upregulation of 3-hydroxy-3-methylglutaryl-CoA synthase and fidgetin-like 1 and downregulation of annexin II, HSP 47 and proteasome α1 occurred in the CuO NPs exposed groups. Taken together, this study provides additional insight into pulmonary cytotoxicity and immunotoxicity as well as oxidative stress in rats exposed to CuO NPs. Proteomic analysis revealed potential toxicological biomarkers of CuO NPs, which also reveals the toxicity mechanisms of CuO NPs.

The fidgetin family: Shaking things up among the microtubule‐severing enzymes

“…Ma et al, 2017). Although not a neoplastic condition, FL1 expression also increases in bronchial epithelial cells in response to DNA damage due to exposure to CuO nanoparticles, with similar effects as seen in non-small cell lung cancer: promotion of cell proliferation and migration and suppression of G1 phase arrest and apoptosis (Kwon et al, 2022).…”

“…In small cell lung cancer cells, where FL1 expression is also increased, knockdown of FL1 increases the effectiveness of the chemotherapeutics etoposide and cisplatin by decreasing tumor cell homologous repair mechanisms (J. Ma et al, 2017). Although not a neoplastic condition, FL1 expression also increases in bronchial epithelial cells in response to DNA damage due to exposure to CuO nanoparticles, with similar effects as seen in non‐small cell lung cancer: promotion of cell proliferation and migration and suppression of G1 phase arrest and apoptosis (Kwon et al, 2022).…”

Roles of Nrf2/HO-1 and ICAM-1 in the Protective Effect of Nano-Curcumin against Copper-Induced Lung Injury

“…MDA is the most prominent byproduct of lipid peroxidation, and it crosslinks to tissue DNA or protein to form adducts, resulting in biomolecular damage [ 46 ]. GSH is a non-enzymatic antioxidant defense that acts directly on free radicals by quenching their reactivity, thus protecting cells from their destructive consequences, or indirectly by activating detoxification enzymes such as glutathione peroxidases, glutathione S-transferases, and glyoxalases [ 47 , 48 , 49 ]. SOD is an enzymatic antioxidant found in most organs, including the brain, liver, thyroid, and lungs.…”

Prolyl oligopeptidase inhibition ameliorates experimental pulmonary fibrosis both in vivo and in vitro

“…The cell count in BALF was carried out as previously described [ 30 ]. Briefly, BALF was collected by cannulating the trachea and lavaging the lung twice with 0.7 mL of phosphate- buffered saline (PBS).…”