Thompson Chad M, Grafström Roland C
National Center for Environmental Assessment, Office of Research and Development, U.S. Environmental Protection Agency, Washington, DC, USA.
J Toxicol Environ Health A. 2008;71(3):244-8. doi: 10.1080/15287390701598259.
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.
长期以来，人们一直怀疑吸入甲醛气体会通过刺激机制导致气道病理生理变化，如哮喘和高反应性。最近关于哮喘和气道生物学的研究表明，一氧化氮（NO）代谢的改变与甲醛的不良反应有关，主要是因为内源性支气管扩张剂S-亚硝基谷胱甘肽（GSNO）的酶促还原依赖于GSNO还原酶（以前称为乙醇脱氢酶-3，ADH3），而该酶也是甲醛细胞解毒的主要酶。鉴于最近的证据表明，像GSNO这样的支气管扩张剂的调节在哮喘中可能比炎症本身发挥更重要的作用，甲醛也需要被视为影响ADH3介导的GSNO分解代谢。这是由于几种潜在机制中ADH3辅因子和硫醇氧化还原状态的变化。数据表明，GSNO周转失调提供了一种基于酶的合理机制，甲醛可能通过该机制加剧哮喘并诱发支气管收缩。
