AN IN VITRO APPROACH TO ASSESS THE TOXICITY OF INHALED TOBACCO SMOKE COMPONENTS: NICOTINE, CADMIUM, FORMALDEHYDE AND URETHANE.
This study by researchers at Cardiff University demonstrated that MatTek’s EpiAirway human airway in vitro tissue model is an excellent tool for screening the toxicity of inhaled compounds. One of the first lines of defence to inhaled toxins is the barrier formed by the tracheobronchial epithelium, making this the ideal region for studying the toxicity of inhaled substances. This study utilises a highly differentiated, three-dimensional, in vitro model of human upper respiratory tract epithelium (EpiAirway AIR-100, MatTek Corp.) to measure the acute toxicological responses to well-characterised tobacco smoke components. To determine the suitability of this model for screening inhaled toxicants, researchers at Cardiff University treated the EpiAirway tissue model apically with tobacco smoke components (nicotine, formaldehyde, cadmium, urethane) which are known to induce a variety of toxic effects (e.g. cytotoxic, thrombogenic, carcinogenic). A range of concentrations were used to model different mechanisms and severity of toxicity which were then compared to known in vivo responses. Similar trends in stress response occurred, with distinct alterations to the EpiAirway tissue in response to all four toxins. At high concentrations, cell viability decreased and tight junctions were degraded, but at sub-toxic concentrations epithelial resistance (indicating tissue integrity) increased 20–60% from control. This peak in resistance coincided with an increase in secreted protein levels, elevated cytokine release and goblet cell hyperplasia and hypertrophy. In conclusion, acute exposure to tobacco smoke components induces measurable toxic responses within human respiratory epithelium. Sub-toxic concentrations appear to illicit a protective response by increasing mucus secretion and mediating immune responses via cytokine release. These responses are comparable to human in vivo responses, indicating potential for the EpiAirway tissue model as a tool for screening the toxicity of inhaled compounds.
Apical surface wash, Bradford assay, Cell viability , Cytokine release , EpiAirway, GM-CSF, Goblet cell hyperplasia, Histology, Hypertrophy, IFN-gamma, IL-10, IL-1a, IL-1b, IL-6, IL-7, Inhaled toxins, MTT, Mucus secretion, Secreted protein, TEER, Tight junctions, Tissue thickening, Tobacco smoke, Trans-epithelial electrical resistance
Cadmium, Cadmium chloride, Formaldehyde, Nicotine, Urethane
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