Isabella Santos de Genaro1, Francine Maria de Almeida2, Fernanda Degobbi Tenorio Quirino Dos Santos Lopes3, Deborah De Camargo Hizume Kunzler4, Bruna Gabryela Busoletto Tripode5, Adriana Kurdejak5, Bruna Nakamura Cordeiro6, Renata Pandolpho5, Mariangela Macchione7, Thayse Regina Brüggemann8, Rodolfo Paula Vieira9, Milton Arruda Martins2, Iolanda de Fátima Lopes Calvo Tibério2, Beatriz Mangueira Saraiva-Romanholo10. 1. Public Employee of Sao Paulo Hospital (IAMSPE), Sao Paulo, Brazil; Department of Medicine (LIM 20), School of Medicine, University of Sao Paulo (FMUSP), Sao Paulo, Brazil. 2. Department of Medicine (LIM 20), School of Medicine, University of Sao Paulo (FMUSP), Sao Paulo, Brazil. 3. Department of Medicine (LIM 20), School of Medicine, University of Sao Paulo (FMUSP), Sao Paulo, Brazil; Institute of LIM's Clinic Hospital of School of Medicine, University of Sao Paulo (FMUSP), Sao Paulo, Brazil. 4. Department of Physical Therapy (LaPEx), State University of Santa Catarina, Florianópolis, Brazil. 5. University City of Sao Paulo (UNICID), Sao Paulo, Brazil. 6. University of Business and Social Sciences (UCES), Buenos Aires, Argentina; University of Mogi das Cruzes, Sao Paulo, Brazil. 7. Department of pathology, Laboratory of Air Pollution, School of Medicine, University of Sao Paulo, Sao Paulo, Brazil. 8. Department of Medicine (LIM 20), School of Medicine, University of Sao Paulo (FMUSP), Sao Paulo, Brazil; Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. 9. Post-graduation Program in Bioengineering and in Biomedical Engineering, Brazil University, São Paulo, Brazil; Brazilian Institute of Teaching and Research in Pulmonary and Exercise Immunology (IBEPIPE), São José dos Campos, Brazil; Post-graduation Program in Sciences of Human Movement and Rehabilitation, Federal University of São Paulo (UNIFESP), Santos, Brazil; Anhembi Morumbi University, School of Medicine, São José dos Campos, SP, Brazil. 10. Public Employee of Sao Paulo Hospital (IAMSPE), Sao Paulo, Brazil; Department of Medicine (LIM 20), School of Medicine, University of Sao Paulo (FMUSP), Sao Paulo, Brazil; University City of Sao Paulo (UNICID), Sao Paulo, Brazil. Electronic address: beatriz.msaraiva@fm.usp.br.
Abstract
AIM: To explore the different consequences of acute and chronic exposure to chlorine gas (Cl2) on the functional and histological parameters of health mice. MAIN METHODS: Firstly, male BALB/c mice were acute exposed to 3.3 or 33.3 or 70.5 mg/m3 Cl2. We analyzed the lung function, the inflammatory cells in the bronchoalveolar lavage, cell influx in the peribrochoalveolar space and mucus production. In a second phase, mice were chronic exposed to 70.5 mg/m3 Cl2. Besides the first phase analyses, we also evaluated the epithelial cells thickness, collagen deposition in the airways, immunohistochemistry stain for IL-1β, iNOS, IL-17 and ROCK-2 and the levels of IL-5, IL-13, IL-17, IL-1β and TNF-α in lung homogenate. KEY FINDINGS: Acute exposure to chlorine impaired the lung function, increased the number of inflammatory cells in the BALF and in the airways, also increased the mucus production. Furthermore, when chlorine was exposed chronically, increased the airway remodeling with collagen deposition and epithelial cells thickness, positive cells for IL-1β, iNOS, IL-17 in the airways and in the alveolar walls and ROCK-2 in the alveolar walls, lung inflammation with increased levels of IL-5, IL-13, IL-1β and TNF-α in the lung homogenate, and also, induced the acid mucus production by the nasal epithelium. SIGNIFICANCE: Acute and chronic exposure to low dose of chlorine gas worsens lung function, induces oxidative stress activation and mucus production and contributes to augmenting inflammation in health mice.
AIM: To explore the different consequences of acute and chronic exposure to chlorine gas (Cl2) on the functional and histological parameters of health mice. MAIN METHODS: Firstly, male BALB/c mice were acute exposed to 3.3 or 33.3 or 70.5 mg/m3 Cl2. We analyzed the lung function, the inflammatory cells in the bronchoalveolar lavage, cell influx in the peribrochoalveolar space and mucus production. In a second phase, mice were chronic exposed to 70.5 mg/m3 Cl2. Besides the first phase analyses, we also evaluated the epithelial cells thickness, collagen deposition in the airways, immunohistochemistry stain for IL-1β, iNOS, IL-17 and ROCK-2 and the levels of IL-5, IL-13, IL-17, IL-1β and TNF-α in lung homogenate. KEY FINDINGS: Acute exposure to chlorine impaired the lung function, increased the number of inflammatory cells in the BALF and in the airways, also increased the mucus production. Furthermore, when chlorine was exposed chronically, increased the airway remodeling with collagen deposition and epithelial cells thickness, positive cells for IL-1β, iNOS, IL-17 in the airways and in the alveolar walls and ROCK-2 in the alveolar walls, lung inflammation with increased levels of IL-5, IL-13, IL-1β and TNF-α in the lung homogenate, and also, induced the acid mucus production by the nasal epithelium. SIGNIFICANCE: Acute and chronic exposure to low dose of chlorine gas worsens lung function, induces oxidative stress activation and mucus production and contributes to augmenting inflammation in health mice.