Generation of oxidant response to copper and iron nanoparticles and salts: Stimulation by ascorbate

Abstract

The present work describes a two-stage approach to analyzing combustion-generated samples for their potential to produce oxidant stress. This approach is illustrated with the two commonly encountered transition metals, copper and iron. First, their abilities to generate hydroxyl radical were measured in a cell-free, phosphate-buffered saline solution containing ascorbate and/or citrate. Second, their abilities to induce heme oxygenase-1 in cultured human epidermal keratinocytes were assessed in cell culture. Combustion-generated copper oxide nanoparticles were active in both assays and were found to be soluble in culture medium. Depletion of glutathione in the cells or loading the cells with ascorbate greatly increased heme oxygenase-1 induction in the presence of copper. By contrast, iron oxide nanoparticles were active in the phosphate buffered saline but not in cell culture, and they aggregated in culture medium. Soluble salts of copper and iron exhibited the same contrast in activities as the respective combustion-generated particles. The results suggest that the capability of combustion-generated environmental samples to produce oxidant stress can be screened effectively in a two step process, first in phosphate buffered saline with ascorbate and subsequently in epithelial cell culture for those exhibiting activity initially. The results also point to an unanticipated interaction in cells of oxidant stress-generating metals with an anti-oxidant (ascorbate) that is usually missing in culture medium formulations. Thus, ascorbate supplementation of cultured human cells is likely to improve their ability to model the in vivo effects of particulate matter containing copper and other redox-active metals.

Fibroblast Response to Lanthanoid Metal Ion Stimulation: Potential Contribution to Fibrotic Tissue Injury

“…Exposure to dusts and particles of various metals is associated with fibrotic changes in the lung [44, 45]. The generally held view is that phagocytosis of inhaled particles by tissue inflammatory cells leads to generation of oxidants and pro-inflammatory cytokines, which, in turn, promote inflammation and tissue damage [44, 45, 53]. As part of the repair process (normal or fibrotic), resident fibrogenic cells, as well as circulating precursors (fibrocytes), are activated by inflammatory mediators to differentiate into myofibroblasts with enhanced collagen-producing capability [54-56].…”

To duckweeds (Landoltia punctata), nanoparticulate copper oxide is more inhibitory than the soluble copper in the bulk solution

“…Synthesis and characterization methods followed Rice et al (2009). In brief, copper oxide nanoparticles were synthesized in the gas phase by introducing the vapor of the metal precursor into a hydrogen/air diffusion flame.…”

Clusterin (Apolipoprotein J), a Molecular Chaperone That Facilitates Degradation of the Copper-ATPases ATP7A and ATP7B

“…Oxidative Stress Promotes Clusterin Interaction with ATP7B-Clusterin activity is initiated in response to cellular stresses (17,20), and both copper excess and deficiency are known to cause oxidative stress in cells (31,32). To determine whether the interaction is modulated directly by oxidative stress, co-immunoprecipitation experiments were repeated using HepG2 cells treated with either H 2 O 2 (20 min) or diamide (15 min) (Fig.…”