An in vitro liver model - assessing oxidative stress and genotoxicity following exposure of hepatocytes to a panel of engineered nanomaterials
Particle and Fibre Toxicology
An in vitro liver model - assessing oxidative stress and genotoxicity following exposure of hepatocytes to a panel of engineered nanomaterials
Ali Kermanizadeh 0
Birgit K Gaiser 0
Gary R Hutchison 1
Vicki Stone 0
0 Heriot-Watt University, School of Life Sciences, Nanosafety Research Group , Edinburgh EH14 4AS , UK
1 Edinburgh Napier University, School of Life, Sport and Social Sciences , Sighthill Campus, Sighthill Court, Edinburgh EH11 4BN , UK
Background: Following exposure via inhalation, intratracheal instillation or ingestion some nanomaterials (NM) have been shown to translocate to the liver. Since oxidative stress has been implicated as a possible mechanism for NM toxicity this study aimed to investigate the effects of various materials (five titanium dioxide (TiO2), two zinc oxide (ZnO), two multi-walled carbon nanotubes (MWCNT) and one silver (Ag) NM) on oxidative responses of C3A cell line as a model for potential detrimental properties of nanomaterials on the liver. Results: We noted a dose dependant decrease in the cellular glutathione content following exposure of the C3A cells to Ag, the ZnO and the MWCNTs. Intracellular ROS levels were also measured and shown to increase significantly following exposure of the C3A to the low toxicity NMs (MWCNT and TiO2). The antioxidant Trolox in part prevented the detrimental effect of NMs on cell viability, and decreased the NM induced IL8 production after exposure to all but the Ag particulate. Following 4 hr exposure of the C3A cells to sub-lethal levels of the NMs, the largest amount of DNA damage was induced by two of the TiO2 samples (7 nm and the positively charged 10 nm particles). Conclusions: All ten NMs exhibited effects on the hepatocyte cell line that were at least in part ROS/oxidative stress mediated. These effects included mild genotoxicity and IL8 production for all NM except the Ag possibly due to its highly cytotoxic nature.
Liver; Nanomaterials; Oxidative stress; Antioxidant; Genotoxicity
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Background
As the field of nanotechnology develops, there are now
over 1300 consumer products on the market with a
claim to contain elements of nanotechnology [1]. The
potential for public and occupational exposure is
therefore likely to increase, and so there is an urgent necessity
to consider the possibility of any detrimental health
consequences with this increased exposure to nanomaterials.
This is achieved in the form of a critical risk assessment
conducted as part of a large consortium (FP7 project
ENPRA Risk Assessment of Engineered Nanoparticle).
The risk is assessed based upon the level of exposure to
the manufactured NM, toxicity of the particle in
question, route of exposure and the persistence in the
organism of the particular material. Hence it is crucial to
identify the hazards associated with NM exposure both
in vitro and in vivo, consequently assembling a
knowledge base of the human health effects associated with
NM exposure [2]. Engineered nanomaterials are
manufactured from a diverse group of substances each with
an array of unique physicochemical characteristics,
hence a varied range of materials need to be evaluated
for a comprehensive toxicity profile allowing for a
structure activity relationship to be generated. It is likely that
NMs will differ in the levels of toxicity induced and the
mechanism by which they exert these adverse effects.
Therefore we investigated a panel of ten widely used
nanomaterials (five different TiO2, two MWCNTs, two
ZnO and one Ag).
The lungs and the gastrointestinal tract are in constant
contact with the external environment so it is not
surprising to find these systems being primary exposure
sites for NMs [3,4]. It is believed that NMs administered
via the ingestion, inhalation or intravenous injection
might eventually reach secondary tissues, one of which
is the liver [5,6].
The liver is the metabolic centre of the body [6]. It has
a crucial role in metabolic homeostasis, as it is
responsible for the storage, synthesis, metabolism and
redistribution of carbohydrates, fats and vitamins. It also
produces large numbers of serum proteins and an array
of enzymes and cytokines [7]. The liver receives and
accumulates materials at much higher volumes
compared to other organs and alongside the kidneys might
be responsible for the clearance of NMs from the blood
[6,8,9]. Previous studies have shown that the uptake and
translocation of TiO2 NMs following intratracheal
instillation has resulted in accumulation of nanomaterials
within the liver [8-10].
There is an abundant body of evidence suggesting the
involvement of oxidative stress in the pathogenesis of
various disorders and diseases. Reactive oxygen species
(ROS) and other free radicals are critical intermediates
in the normal physiology and pathophysiology of the
liver [5]. Oxygen species are important in the creation of
oxidative stimuli required for normal physiologic
homeostasis of hepatocytes, as well as playing (...truncated)