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Effects of formaldehyde exposure on the development of pulmonary fibrosis induced by bleomycin in mice.

ABSTRACT: Environmental and Occupational pollution has been extensively studied because of its serious implications on the human health. Formaldehyde (FA) is a pollutant widely employed in several industries and also in anatomy, pathology and histology laboratories. Studies have shown the correlation between FA exposure and development or worsening of asthma. However, the effect of FA exposure on the pulmonary fibrosis (PF) is unknown. PF is a progressive and chronic lung disease with high incidence and considerable morbidity and mortality. Few studies have shown a worsening of PF after pollutants exposure such as ozone and nitrogen dioxide. Therefore, our objective was to assess the effects of FA on the PF. Male mice C57BL6 were treated or not with bleomycin (1,5?U/kg) and exposed or not to FA inhalation (0.92?mg/m3, 1?h/day, 5 days/week during 2 weeks). Non-manipulated mice were used as control. Our data showed that FA exposure in fibrotic mice increased the number of granulocytes in the bronchoalveolar lavage followed by elevated levels of interleukin 1 beta and interleukin 17. In addition, FA exposure in fibrotic mice enhanced the gene expression of C-X-C motif chemokine ligand 1 (CXCL1) and tumor necrosis factor alpha (TNF-?) in the lung. We also showed an increase in the collagen production, while lung elastance was reduced. No differences were found in the mucus production, oedema and interstitial thickening in the lung tissue of fibrotic mice after FA exposure. In conclusion our study showed that FA exposure aggravates the lung neutrophils influx and collagen production, but did not alter the lung elastance, mucus production, oedema and interstitial tickening. This work contributes to understand the effects of pollution in the development of PF.

SUBMITTER: Leal MP

PROVIDER: S-EPMC5977414 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Effects of formaldehyde exposure on the development of pulmonary fibrosis induced by bleomycin in mice.

Leal Mayara Peres MP Brochetti Robson Alexandre RA Ignácio Aline A Câmara Niels Olsen Saraiva NOS da Palma Renata Kelly RK de Oliveira Luis Vicente Franco LVF de Fátima Teixeira da Silva Daniela D Lino-Dos-Santos-Franco Adriana A

Toxicology reports 20180405

Environmental and Occupational pollution has been extensively studied because of its serious implications on the human health. Formaldehyde (FA) is a pollutant widely employed in several industries and also in anatomy, pathology and histology laboratories. Studies have shown the correlation between FA exposure and development or worsening of asthma. However, the effect of FA exposure on the pulmonary fibrosis (PF) is unknown. PF is a progressive and chronic lung disease with high incidence and c ...[more]

PMID: 29854623

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Project description:BACKGROUND: Pulmonary fibrosis (PF) is a group of devastating and largely irreversible diseases. Phosphodiesterase (PDE) 4 is involved in the processes of remodeling and inflammation, which play key role in tissue fibrosis. The aim of the study was, therefore, to investigate the effect of PDE4 inhibition in experimental model of PF. METHODS: PF was induced in C57BL/6N mice by instillation of bleomycin. Pharmacological inhibition of PDE4 was achieved by using cilomilast, a selective PDE4 inhibitor. Changes in either lung inflammation or remodeling were evaluated at different stages of experimental PF. Lung inflammation was assessed by bronchoalveolar lavage fluid (BALF) differential cell count and reverse transcription quantitative polymerase chain reaction (RT-qPCR) for inflammatory cytokines. Changes in tissue remodeling were evaluated by pulmonary compliance measurement, quantified pathological examination, measurement of collagen deposition and RT-qPCR for late remodeling markers. Survival in all groups was analyzed as well. RESULTS: PDE4 inhibition significantly reduced the total number of alveolar inflammatory cells in BALF of mice with bleomycin-induced PF at early fibrosis stage (days 4 and 7). Number of macrophages and lymphocytes, but not neutrophils, was significantly reduced as well. Treatment decreased lung tumor necrosis factor (TNF)-alpha mRNA level and increased mRNA level of interleukin (IL)-6 but did not influence IL-1 beta. At later stage (days 14 and 24) cilomilast improved lung function, which was shown by increase in lung compliance. It also lowered fibrosis degree, as was shown by quantified pathological examination of Hematoxilin-Eosin stained lung sections. Cilomilast had no significant effect on the expression of late remodeling markers such as transforming growth factor (TGF)-beta1 and collagen type Ia1 (COL(I)alpha1). However, it tended to restore the level of lung collagen, assessed by SIRCOL assay and Masson's trichrome staining, and to improve the overall survival. CONCLUSIONS: Selective PDE4 inhibition suppresses early inflammatory stage and attenuates the late stage of experimental pulmonary fibrosis.

Dataset Information

Effects of formaldehyde exposure on the development of pulmonary fibrosis induced by bleomycin in mice.

Publications

Effects of formaldehyde exposure on the development of pulmonary fibrosis induced by bleomycin in mice.

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