Mechanistic considerations for formaldehyde-induced bronchoconstriction involving S-nitrosoglutathione reductase.
Inhalation of formaldehyde vapor has long been suspected of producing airway pathophysiology such as asthma and hyperresponsivity, presumably via irritant mechanisms. Recent studies on asthma and airway biology implicate changes in nitric oxide (NO) disposition in the adverse effects of formaldehyde, principally because enzymatic reduction of the endogenous bronchodilator S-nitrosoglutathione (GSNO) is dependent upon GSNO reductase (formally designated as alcohol dehydrogenase-3, ADH3), which also serves as the primary enzyme for cellular detoxification of formaldehyde. Considering recent evidence that regulation of bronchodilators like GSNO might play a more important role in asthma than inflammation per se, formaldehyde also needs to be considered as influencing ADH3-mediated GSNO catabolism. This is due to changes in ADH3 cofactors and thiol redox state among several potential mechanisms. Data suggest that deregulation of GSNO turnover provides a plausible, enzymatically based mechanism by which formaldehyde might exacerbate asthma and induce bronchoconstriction.
D000445:Aldehyde Oxidoreductases / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D001249:Asthma / Q000139:chemically induced* / Q000201:enzymology; D016084:Bronchoconstriction / Q000187:drug effects*; D004202:Disinfectants / Q000009:adverse effects*; D005557:Formaldehyde / Q000009:adverse effects*; D006801:Humans
D004202:Disinfectants; D005557:Formaldehyde; D000445:Aldehyde Oxidoreductases; C087006:formaldehyde dehydrogenase, glutathione-independent