125,515 research outputs found
Mimicking cigarette smoke exposure to assess cutaneous toxicity
No full textCigarette smoke stands among the most toxic environmental pollutants and is composed of thousands of chemicals including polycyclic aromatic hydrocarbons (PAHs). Despite restrict cigarette smoking ban in indoor or some outdoor locations, the risk of non-smokers to be exposed to environmental cigarette smoke is not yet eliminated. Beside the well-known effects of cigarette smoke to the respiratory and cardiovascular systems, a growing literature has shown during the last 3 decades its noxious effects also on cutaneous tissues. Being the largest organ as well as the interface between the outer environment and the body, human skin acts as a natural shield which is continuously exposed to harmful exogenous agents. Thus, a prolonged and/or repetitive exposure to significant levels of toxic smoke pollutants may have detrimental effects on the cutaneous tissue by disrupting the epidermal barrier function and by exacerbating inflammatory skin disorders (i.e. psoriasis, atopic dermatitis). With the development of very complex skin tissue models and sophisticated cigarette smoke exposure systems it has become important to better understand the toxicity pathways induced by smoke pollutants in more realistic laboratory conditions to find solutions for counteracting their effects. This review provides an update on the skin models currently available to study cigarette smoke exposure and the known pathways involved in cutaneous toxicity. In addition, the article will briefly cover the inflammatory skin pathologies potentially induced and/or exacerbated by cigarette smoke exposure
Silica nanoparticles and their interaction with cells : a multidisciplinary approach
No full textSilica nanoparticles are increasingly used as drug delivery systems and for biomedical imaging.
Therapeutic and diagnostic agents can be incorporated into the silica matrix to improve the stability
and solubility of hydrophobic drugs in biological systems. However, the safety of silica
nanoparticles as drug carriers remains controversial. To date, no validated and accepted nanospecific
tests exist to predict the potentially harmful impact of these materials on the human body.
The mechanism proposed for hemolysis of unmodified silica nanoparticles is based on the electrostatic
interaction between the silanol surface groups and the quaternary ammonium in the choline
head group of the phospholipids. However, a detailed understanding of this process is missing.
In this thesis, different silica nanoparticles where synthesized, characterized, and tested in two cell
lines regarding viability and oxidative stress. Hemolysis was assessed using red blood cells. Furthermore,
the hemolytic mechanism of a chosen silica nanoparticle type was investigated in depth
using a biophysical chemistry approach. We used the dye-leakage assay, isothermal titration
calorimetry, solid state nuclear magnetic resonance, and flow cytometry to elucidate this mechanism.
Our results revealed that silica nanoparticles with a porous surface and negative surface charge
had the strongest impact on viability in a concentration dependent manner. This is in contrast to
non-porous silica nanoparticles. None of the studied particles caused oxidative stress in either cell
lines. Particles with a negative surface charge induced hemolysis. The mechanism responsible for
the hemolysis for silica nanoparticles had no electrostatic component. The nuclear magnetic resonance
data revealed no interaction with the choline group. However, nuclear magnetic resonance
data suggested the presence of faster tumbling species.
Our toxicological and mechanistic studies showed potential hazards of spherical amorphous silica
nanoparticles. Physico-chemical properties mediating toxicity in living cells were identified.
We propose that our standardized silica nanoparticles may serve as a readily available reference
material for nanotoxicological investigations. Mechanistic data did not support an electrostatic
interaction as postulated in the literature, but rather a strong adsorption process that may lead
to hemolysis. Furthermore, the presence of faster tumbling species suggested the formation of
smaller lipid bilayer structures upon silica nanoparticles exposure. Flow cytometry data revealed
that their size is about 100 nm. It remains to be proven if the bilayer wraps around the hemolytic
silica nanoparticles, if an exclusive formation of smaller species without wrapping is present, or
both of the aforementioned
Cultivating a three-dimensional reconstructed human epidermis at a large scale
No full textA three-dimensional human epidermis model reconstructed from neonatal primary keratinocytes is presented. Herein, a protocol for the cultivation process and the characterization of the model is described. Neonatal primary keratinocytes are grown submerged on permeable polycarbonate inserts and lifted to the air-liquid interface three days after seeding. After fourteen days of stimulation with defined growth factors and ascorbic acid in high calcium culture medium, the model is fully differentiated. Histological analysis revealed a completely stratified epidermis, mimicking the morphology of native human skin. To characterize the model and its barrier functions, protein levels and localization specific for early-stage keratinocyte differentiation (i.e., keratin 10), late-stage differentiation (i.e., involucrin, loricrin, and filaggrin) and tissue adhesion (i.e., desmoglein 1), were assessed by immunofluorescence. The tissue barrier integrity was further evaluated by measuring transepithelial electrical resistance. Reconstructed human epidermis was responsive to proinflammatory stimuli (i.e., lipopolysaccharide and tumor necrosis factor alpha), leading to increased cytokine release (i.e., interleukin 1 alpha and interleukin 8). This protocol represents a straightforward and reproducible in vitro method to cultivate reconstructed human epidermis as a tool to assess environmental effects and a broad range of skin-related studies
Investigating nanoparticle mutagenicity: Can nanoparticle-bacterial interactions provide an insight into the unknown?
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