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Cholinergic hypofunction effects in the mechanical and lung histopathology in an experimental model of lung inflammation induced by air pollutant instillation in mice

Grant number: 11/15817-7
Support type:Scholarships in Brazil - Master
Effective date (Start): March 01, 2012
Effective date (End): February 28, 2014
Field of knowledge:Biological Sciences - Physiology
Principal Investigator:Carla Máximo Prado
Grantee:Fernanda Paula Roncon Santana
Home Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil


The diesel engines widely used in urban centers and this burning is considered major environmental pollutant and toxic to human health. Due to its chemical characteristic, the diesel particles reach distal airways that can cause lung inflammation and worse diseases such as bronchial asthma and pulmonary emphysema. Results obtained by our group showed a worsened effect of the disability cholinergic function and inflammation in animals that already had allergic pulmonary inflammation; through these data our objective in this study is evaluate the effects of cholinergic hypofunction in the functional and histopathological changes induced for repeated pulmonary instillation of diesel. For this study will be used male mice genetically modified to a reduced expression of vesicular acetylcholine transporter protein (VAChT). The animals will be divided into groups: homozygous (HOM) and wild (WT). Each group will receive intranasal instillation of diesel dust (DEP) for 30 days 5x per week. It will be analyzed: changes in respiratory mechanics, lung remodeling, inflammatory response, immunohistochemistry and Elisa. Based on the data from the literature of the importance of the cholinergic system in the inflammatory response and preliminary data from our research group, it is expected that homozygous animals have worsening of the inflammatory response induced by DEP confirming the participation of the cholinergic system in the inflammatory process.

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
SANTANA, FERNANDA P. R.; PINHEIRO, NATHALIA M.; BITTENCOURT-MERNAK, MARCIA I.; PERINI, ADENIR; YOSHIZAKI, KELLY; MACCHIONE, MARIANGELA; SALDIVA, PAULO H. N.; MARTINS, MILTON A.; TIBERIO, IOLANDA F. L. C.; PRADO, MARCO ANTONIO M.; PRADO, VANIA F.; PRADO, CARLA M. Vesicular acetylcholine transport deficiency potentiates some inflammatory responses induced by diesel exhaust particles. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY, v. 167, p. 494-504, JAN 15 2019. Web of Science Citations: 2.
SANTANA, FERNANDA PAULA R.; PINHEIRO, NATHALIA M.; MERNAK, MARCIA ISABEL B.; RIGHETTI, RENATO F.; MARTINS, MILTON A.; LAGO, JOAO H. G.; DOS SANTOS LOPES, FERNANDA D. T. Q.; TIBERIO, IOLANDA F. L. C.; PRADO, CARLA M. Evidences of Herbal Medicine-Derived Natural Products Effects in Inflammatory Lung Diseases. Mediators of Inflammation, 2016. Web of Science Citations: 9.
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
SANTANA, Fernanda Paula Roncon. Effects of cholinergic hipofunction in lung mechanics and histopathology in an experimental model of lung inflammation induced by air pollution in mice. 2014. Master's Dissertation - Universidade de São Paulo (USP). Faculdade de Medicina São Paulo.

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