5 research outputs found
In Search of the Chemical Basis of the Hemolytic Potential of Silicas
The
membranolytic activity of silica particles toward red blood
cells (RBCs) has been known for a long time and is sometimes associated
with silica pathogenicity. However, the molecular mechanism and the
reasons why hemolysis differs according to the silica form are still
obscure. A panel of 15 crystalline (pure and commercial) and amorphous
(pyrogenic, precipitated from aqueous solutions, vitreous) silica
samples differing in size, origin, morphology, and surface chemical
composition were selected and specifically prepared. Silica particles
were grouped into six groups to compare their potential in disrupting
RBC membranes so that one single property differed in each group,
while other features were constant. Free radical production and crystallinity
were not strict determinants of hemolytic activity. Particle curvature
and morphology modulated the hemolytic effect, but silanols and siloxane
bridges at the surface were the main actors. Hemolysis was unrelated
to the overall concentration of silanols as fully rehydrated surfaces
(such as those obtained from aqueous solution) were inert, and one
pyrogenic silica also lost its membranolytic potential upon progressive
dehydration. Overall results are consistent with a model whereby hemolysis
is determined by a defined surface distribution of dissociated/undissociated
silanols and siloxane groups strongly interacting with specific epitopes
on the RBC membrane
Hematite Nanoparticles Larger than 90 nm Show No Sign of Toxicity in Terms of Lactate Dehydrogenase Release, Nitric Oxide Generation, Apoptosis, and Comet Assay in Murine Alveolar Macrophages and Human Lung Epithelial Cells
Three hematite samples were synthesized by precipitation
from a
FeCl<sub>3</sub> solution under controlled pH and temperature conditions
in different morphology and dimensions: (i) microsized (average diameter
1.2 μm); (ii) submicrosized (250 nm); and (iii) nanosized (90
nm). To gain insight into reactions potentially occurring <i>in vivo</i> at the particle–lung interface following
dust inhalation, several physicochemical features relevant to pathogenicity
were measured (free radical generation in cell-free tests, metal release,
and antioxidant depletion), and cellular toxicity assays on human
lung epithelial cells (A549) and murine alveolar macrophages (MH-S)
were carried out (LDH release, apoptosis detection, DNA damage, and
nitric oxide synthesis). The decrease in particles size, from 1.2
μm to 90 nm, only caused a slight increase in structural defects
(disorder of the hematite phase and the presence of surface ferrous
ions) without enhancing surface reactivity or cellular responses in
the concentration range between 20 and 100 μg cm<sup>–2</sup>
Additional file 1: Figure S1. of Revisiting the paradigm of silica pathogenicity with synthetic quartz crystals: the role of crystallinity and surface disorder
Particle size distribution curves of the quartz crystals studied measured with DCS technique. Figure S2. Bio-TEM images of quartz samples internalized by RAW 264.7 murine macrophages. Figure S3. Size characterization curve of liposome dispersion measured by DLS. Table S1. Curve-fit parameters calculated by fitting experimental dataset (Μ potential vs pH) with a Boltzmann equation. (DOCX 952 kb
Surface Reactivity and Cell Responses to Chrysotile Asbestos Nanofibers
High aspect-ratio nanomaterials (HARNs) have recently
attracted
great attention from nanotoxicologists because of their similarity
to asbestos. However, the actual risk associated with the exposure
to nanosized asbestos, which escapes most regulations worldwide, is
still unknown. Nanometric fibers of chrysotile asbestos have been
prepared from two natural sources to investigate whether nanosize
may modulate asbestos toxicity and gain insight on the hazard posed
by naturally occurring asbestos, which may be defined as HARNs because
of their dimensions. Power ultrasound was used to obtain nanofibers
from two different chrysotile specimens, one from the dismissed asbestos
mine in Balangero (Italian Western Alps) and the other from a serpentine
outcrop in the Italian Central Alps. Electron microscopy, X-ray diffraction,
and fluorescence spectroscopy revealed that the procedure does not
affect mineralogical and chemical composition. Surface reactions related
to oxidative stress, free radical generation, bioavailability of iron,
and antioxidant depletion, revealed a consistent reduction in reactivity
upon reduction in size. When tested on A549 human epithelial cells,
the pristine but not the nanosized fibers proved cytotoxic (LDH release),
induced NO production, and caused lipid peroxidation. However, nanofibers
still induced some toxicity relevant oxidative stress activity (ROS
production) in a dose-dependent fashion. The reduction in length and
a lack of poorly coordinated bioavailable iron in nanochrysotile may
explain this behavior. The present study provides a one-step procedure
for the preparation of a homogeneous batch of natural asbestos nanofibers
and shows how a well-known toxic material might not necessarily become
more toxic than its micrometric counterpart when reduced to the nanoscale
The Potential Contribution of Hexavalent Chromium to the Carcinogenicity of Chrysotile Asbestos
Chrysotile asbestos
is a carcinogenic mineral that has abundantly
been used in industrial and consumer applications. The carcinogenicity
of the fibers is partly governed by reactive Fe surface sites that
catalyze the generation of highly toxic hydroxyl radicals (HO•) from extracellular hydrogen peroxide (H2O2). Chrysotile also contains Cr, typically in the low
mass permille range. In this study, we examined the leaching of Cr
from fibers at the physiological lung pH of 7.4 in the presence and
absence of H2O2. Furthermore, we investigated
the potential of cells from typical asbestos-burdened tissues and
cancers to take up Cr leached from chrysotile in PCR expression, immunoblot,
and cellular Cr uptake experiments. Finally, the contribution of Cr
to fiber-mediated H2O2 decomposition and HO• generation was studied. Chromium readily dissolved
from chrysotile fibers in its genotoxic and carcinogenic hexavalent
redox state upon oxidation by H2O2. Lung epithelial,
mesothelial, lung carcinoma, and mesothelioma cells expressed membrane-bound
Cr(VI) transporters and accumulated Cr up to 10-fold relative to the
Cr(VI) concentration in the spiked medium. Conversely, anion transporter
inhibitors decreased cellular Cr(VI) uptake up to 45-fold. Finally,
chromium associated with chrysotile neither decomposed H2O2 nor contributed to fiber-mediated HO• generation. Altogether, our results support the hypothesis that
Cr may leach from inhaled chrysotile in its hexavalent state and subsequently
accumulate in cells of typically asbestos-burdened tissues, which
could contribute to the carcinogenicity of chrysotile fibers. However,
unlike Fe, Cr did not significantly contribute to the adverse radical
production of chrysotile