REVIEW Acrolein – a pulmonary hazard Kiflai Bein à and George D. Leikauf Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA Received: April 25, 2011 Revised: June 17, 2011 Accepted: June 20, 2011 Acrolein is a respiratory irritant that can be generated during cooking and is in environmental tobacco smoke. More plentiful in cigarette smoke than polycyclic aromatic hydrocarbons (PAH), acrolein can adduct tumor suppressor p53 (TP53) DNA and may contribute to TP53- mutations in lung cancer. Acrolein is also generated endogenously at sites of injury, and excessive breath levels (sufficient to activate metalloproteinases and increase mucin tran- scripts) have been detected in asthma and chronic obstructive pulmonary disease (COPD). Because of its reactivity with respiratory-lining fluid or cellular macromolecules, acrolein alters gene regulation, inflammation, mucociliary transport, and alveolar–capillary barrier integrity. In laboratory animals, acute exposures have lead to acute lung injury and pulmonary edema similar to that produced by smoke inhalation whereas lower concentra- tions have produced bronchial hyperreactivity, excessive mucus production, and alveolar enlargement. Susceptibility to acrolein exposure is associated with differential regulation of cell surface receptor, transcription factor, and ubiquitin-proteasome genes. Consequent to its pathophysiological impact, acrolein contributes to the morbidly and mortality associated with acute lung injury and COPD, and possibly asthma and lung cancer. Keywords: ARDS / Asthma / Carbonyl stress / Chronic obstructive pulmonary disease / Countermeasures 1 Introduction Acrolein (2-propenal) is an a-b-unsaturated aldehyde that is volatile at room temperature and is highly irritating to eyes and respiratory passages. Acrolein can be formed by heating cooking oils and fats above 3001C (e.g. wok cooking [1]), and thus its name refers to pungent ‘‘acrid’’ (from Latin stem: acer meaning sharp or sour) smell that is produced from ‘‘oleum’’ (Latin meaning ‘‘oil’’) [2]. Acrolein also can be formed in domestic cooking with biomass fuels [3], and is present in environmental tobacco smoke [2, 4–6], which remains a significant occupational health hazard in the restaurant workplace [7–10]. Additional human exposure can result from acrolein use as a herbicide and through its use as a chemical feedstock. As an a,b-unsaturated aldehyde, acrolein contains a reactive carbonyl group and an electrophilic a-carbon and thus is highly reactive with biological macromolecules [11–14]. Irritant stimuli, of which acrolein is one of the most potent, activate respiratory sensory nerve endings, including Ca 21 -permeable transient receptor potential cation channel, subfamily A, member 1 (TRPA1) [15]. In addition to nasal irritation, acrolein-activated TRPA1 signaling can lead to cough and inflammation [16, 17]. Although irritant-induced sensory responses can serve as warning signs and promote avoidance behavior or adaptation of protective measures, acrolein exposure remains a global health problem because its release is closely linked to basic human needs (e.g. cooking), emergencies (e.g. fire fighting), or personal habits (e.g. smoking). While acrolein can cause adverse effects in several organ systems, this review focuses on inhaled Abbreviations: BAL, bronchoalveolar lavage; COPD, chronic obstructive pulmonary disease; CLDN5, claudin 5; EGFR, epider- mal growth factor receptor; GSH, reduced glutathione; MMP, metalloproteinase à Additional corresponding author: Professor Kiflai Bein E-mail: kbein@pitt.edu Correspondence: Professor George D. Leikauf, Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh, 100 Technology Dr, Suite 350, Pittsburgh, PA 15219-3130, USA E-mail: gleikauf@pitt.edu Fax: 11-412-624-3060 & 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.mnf-journal.com 1342 Mol. Nutr. Food Res. 2011, 55, 1342–1360 DOI 10.1002/mnfr.201100279