title: Formaldehyde induces lung inflammation by an oxidant and antioxidant enzymes mediated mechanism in the lung tissue.
abstract: Formaldehyde (FA) is an indoor and outdoor pollutant widely used by many industries, and its exposure is associated with inflammation and oxidative stress in the airways. Our previous studies have demonstrated the role of reactive oxygen species (ROS) in lung inflammation induced by FA inhalation but did not identify source of the ROS. In the present study, we investigate the effects of FA on the activities and gene expression of glutathione peroxidase (GPX), glutathione reductase (GR), glutathione S-transferase (GST), superoxide dismutase (SOD) 1 and 2, catalase (CAT), nitric oxide synthase (iNOS and cNOS) and cyclooxygenase (COX) 1 and 2. The hypothesized link between NADPH-oxidase, nitric oxide synthase and cyclooxygenase, the lung inflammation after FA inhalation was also investigated. For experiments, male Wistar rats were submitted to FA inhalation (1%, 90 min daily) for 3 consecutive days. The treatments with apocynin and indomethacin before the FA exposure reduced the number of neutrophils recruited into the lung. Moreover, the treatments with apocynin and indomethacin blunted the effect of FA on the generation of IL-1β, while the treatments with L-NAME and apocynin reduced the generation of IL-6 by lung explants when compared to the untreated group. FA inhalation increased the levels of NO and hydrogen peroxide by BAL cells cultured and the treatments with apocynin and l-NAME reduced these generations. FA inhalation did not modify the activities of GPX, GR, GST and CAT but reduced the activity of SOD when compared to the naïve group. Significant increases in SOD-1 and -2, CAT, iNOS, cNOS and COX-1 expression were observed in the FA group compared to the naïve group. The treatments with apocynin, indomethacin and L-NAME reduced the gene expression of antioxidant and oxidant enzymes. In conclusion, our results indicate that FA causes a disruption of the physiological balance between oxidant and antioxidant enzymes in lung tissue, most likely favoring the oxidant pathways and thus positively modulating lung inflammation.
authors: Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors: Adriana
authors: A
authors: Lino-dos-Santos-Franco
authors: Matheus
authors: M
authors: Correa-Costa
authors: Ana Carolina Cardoso dos Santos
authors: AC
authors: Durão
authors: Ana Paula Ligeiro
authors: AP
authors: de Oliveira
authors: Ana Cristina
authors: AC
authors: Breithaupt-Faloppa
authors: Jônatas de Almeida
authors: Jde A
authors: Bertoni
authors: Ricardo Martins
authors: RM
authors: Oliveira-Filho
authors: Niels Olsen Saraiva
authors: NO
authors: Câmara
authors: Tânia
authors: T
authors: Marcourakis
authors: Wothan
authors: W
authors: Tavares-de-Lima
mesh_terms: D000818:Animals; D002374:Catalase / Q000378:metabolism; D005557:Formaldehyde / Q000633:toxicity*; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced* / Q000201:enzymology; D019570:Inhalation Exposure / Q000009:adverse effects; D008168:Lung / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D005557:Formaldehyde; D002374:Catalase; D005979:Glutathione Peroxidase; D019001:Nitric Oxide Synthase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D005982:Glutathione Transferase