Avaliação dos efeitos de irritantes inalatórios no modelo alveolar 3D Tox In-Pulmonar
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2021-03-29
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Universidade Federal de Goiás
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Introduction: The Respiratory System has direct contact with the external environment, making it one of the main entry routes for chemical compounds and/or particles in the human
organism. Inhalation toxicity analyzes are performed through in vivo tests, however, the toxicology of the 21st century seeks to replace, reduce and refine the use of animals in research.
Currently, the emergence of new substances and particles with the most diverse purposes is
increasing, being necessary for the toxicological investigation of these. With the advancement
of science and the emergence of new technologies, some companies have commercially made
available in vitro models for assessing inhalation toxicity, however, these models are not commercially available in Brazil. With this in mind, the research group Tox In developed a 3Dmodel
with human pulmonary alveolar cells A549 (Tox In-Pulmonar) to mimic human exposure
through culture in an air-liquid interface and conduct in vitro inhalation toxicity assessments in
Brazil. Objective: To investigate the effects of exposure of lung cells to inhaledtoxicants directly
on the tissue, using the Tox In-Pulmonar model. Methods: Inhaled toxicantswere prepared
according to the determined concentrations and according to the physical and chemical characteristics of each compound. The construction of the Tox In-Pulmonar model occurred by cultivating the A549 cell in an air-liquid interface. In the present study, the exposure of inhaled
toxicants in liquid form directly on the tissue was evaluated and PBS was used as a negative
control. After exposure, the tissues were incubated in the culture oven at 37ºC for 3 hours and
evaluated using the MTT assay. Morphological evaluation of the Tox In-Pulmonar model was
also performed through histological processing. Results: The results suggest that the Tox InPulmonar model responds to exposure to inhaled toxicants according tothe GHS classification
and that from this model a prediction for LC50 concentrations in animals can be made. Discussion: The model proved to be promising in the responses to inhaled toxicants, obtaining responses similar to the commercially available model EpiAirway. Also, the model can predict the
value of LC50 in animals, which can drastically reduce their use in research. Conclusion: It is
concluded that the 3D alveolar model developed can be a promising alternative to acute inhalation toxicity tests.
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FURTUOSO, M. M. S. Avaliação dos efeitos de irritantes inalatórios no modelo alveolar 3D Tox In-Pulmonar. 2021. 48 f. Dissertação (Mestrado em Ciências Farmacêuticas) - Universidade Federal de Goiás, Goiânia, 2021.