Role Of Transient Receptor Potential Ion Channels And Evoked Levels Of Neuropeptides In A Formaldehyde-Induced Model Of Asthma In Balb/c Mice

Formaldehyde (FA), a kind of popular indoor air pollutant, and it is a global environmental pollutant. The effects of formaldehyde on human health include eyes and upper respiratory irritancy, neurotoxicity, reproductive toxicity, allery and immunological effects, oxidative damage, genotoxicity. Asthma disease rates keep on increasing all over the world, especially in western societies over last40years.Discoveryof risk factors for the rise in asthma cases is essentially important, although some studies have indicated that indoor formaldehyde might worsen allergies andbe an underlying factor for increasing incidence andseverity of asthma, the mechanism was not clear and needs to be further investigated. In order to explore whether formaldehyde could involve in asthma and its molecular mechanism in the process of asthma, experiments in vivo were employed.1. Balb/c mice in three experimental groups were exposed to:(a) vehicle control;(b) formaldehyde (0.5mg/m3);(c) formaldehyde (3.0mg/m3). The mice were exposed to FA for8h and7day respectively. Then evaluate the content of malonyldialdehyde (MDA), glutathione (GSH), interleukin-1β (IL-1β) and substance P in brain and spinal cord.3.0mg/m3formaldehyde exposure led to a significant increase in levels of MDA, IL-1β and substance P, decreases in GSH level in two tissues. The result showed that high concentration of gaseous formaldehyde induced neurotoxicity of central nervous system. The mechanism of it perhaps relate to oxidative damage of brain and spinal cord.2. Balb/c mice in five experimental groups were exposed to:(a) vehicle control;(b) formaldehyde (0.5mg/m3);(c) formaldehyde (1.0mg/m3);(d) formaldehyde (3.0mg/m3);(e) formaldehyde (3.0mg/m3)+HC-030031[antagonist of transient receptor potential ankyrin1(TRPA1)]. The mice were exposed to FA for8h and10day respectively. Then evaluate the content of MDA, superoxide dismutase (SOD) and immunoglobulin E (IgE) in serum, interleukin-4(IL-4) in bronchialveolar lavage fluid.3.0mg/m3formaldehyde exposure led to a significant increase in such biomarker and changes in the levels of biomarker could be inhibited by HC-030031. The result showed that TRPA1receptor channel mediated formaldehyde induced airway inflammation and caused oxidative damage, chronic respiratory disease induced by formaldehyde may associate with the TRPA1receptor channel. 3. The irritant effect and immune adjuvant effect are the two possible pathways for formaldehyde to promote asthma. Balb/c mice in six experimental groups were exposed to:(a) vehicle control;(b) ovalbumin;(c) formaldehyde (3.0mg/m3);(d) ovalbumin+formaldehyde (3.0mg/m3);(e) ovalbumin+formaldehyde (3.0mg/m3)+HC-030031(antagonist of transient receptor potential ankyrin1);(f) ovalbumin+formaldehyde (3.0mg/m3)+capsazepine (antagonist of transient receptor potential vanilloid1). Experiments were conductedafter4weeks of exposure and1-week challenge with aerosolized ovalbumin. Airway hyper-responsiveness, pulmonary tissue damage, eosinophil infiltration, and increased levels of IL-4, IL-1β, IgE, substance P and calcitonin gene-related peptide (CGRP) in lung tissues werefound in the ovalbumin+formaldehyde (3.0mg/m3) group compared with the values seen in ovalbumin-only immunized mice. Except for interleukin-1β levels, other changesin the levels of biomarker could be inhibited by HC-030031and capsazepine. Formaldehyde might be one of key risk factor for the rise in asthma cases. Transient receptor potential ion channels and neuropeptides have important roles in formaldehyde promoted-asthma.