Acrolein—A pulmonary hazard

Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15219-3130, USA.
Molecular Nutrition & Food Research (Impact Factor: 4.6). 09/2011; 55(9):1342-60. DOI: 10.1002/mnfr.201100279
Source: PubMed


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 transcripts) 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 concentrations 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.

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Available from: George D Leikauf, Jun 24, 2014
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    • "In the present work, we subjected cells to oxidative stress to examine the effects of IOnps, which showed negligible influence on cell functions under normal conditions. Acrolein, a well-known respiratory irritant, induces damage in the respiratory system (Bein and Leikauf 2011), central nervous system (shi et al. 2011), cardiovascular system (Anderson et al. 2012), and liver (mohammad et al. 2012). In the present work, we confirmed that acrolein induced a concentration-dependent viability loss in H9c2 cells (Fig. 2b). "
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    ABSTRACT: Superparamagnetic iron oxide nanoparticles (IONPs) have been widely applied in numerous biomedical fields. The evaluation of the toxicity of IONPs to the environment and human beings is indispensable to guide their applications. IONPs are usually considered to have good biocompatibility; however, some literatures have reported the toxicity of IONPs in vitro and in vivo. The controversy surrounding the biocompatibility of IONPs prompted us to carefully consider the biological effects of IONPs, especially under stress conditions. However, the potential risks of IONPs under stress conditions have not yet been evaluated in depth. Acrolein is widespread in the environment and modulates stress-induced gene activation and cell death in many organs and tissues. In this study, we assessed the sensitivity of H9c2 cardiomyocyte cells embedded with IONPs to acrolein and investigated the possible molecular mechanisms involved in this sensitivity. IONPs, which alone exhibited no toxicity, sensitized the H9c2 cardiomyocytes to acrolein-induced dysfunction. The IONP/acrolein treatment induced a loss of viability, membrane disruption, reactive oxygen species (ROS) generation, Erk activation, mitochondrial and lysosomal dysfunction, and necrosis in H9c2 cells. Treatment with an ROS generation inhibitor (diphenyleneiodonium) or an iron chelator (deferoxamine) prevented the IONP/acrolein-induced loss of viability, suggesting that ROS and IONP degradation facilitated the toxicity of the IONP/acrolein treatment in H9c2 cells. Our data suggest that cells embedded in IONPs are more vulnerable to oxidative stress, which confirms the hypothesis that nanoparticles can sensitize cells to the adverse effects of external stimulation. The present work provides a new perspective from which to evaluate the interactions between nanoparticles and cells.
    Full-text · Article · May 2014 · Archive für Toxikologie
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    • "Acrolein's role as a respiratory toxicant is well established [6], [7]. Because of its high reactivity with human tissue, inhalation of acrolein has been hypothesized to induce or exacerbate acute lung injury and chronic obstructive pulmonary disease [21]. A risk assessment for human lung function extrapolated from rat data suggested that ambient concentrations of acrolein in the United States may be associated with reduced respiratory function [35]. "
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    ABSTRACT: Acrolein is an air toxic and highly potent respiratory irritant. There is little epidemiology available, but US EPA estimates that outdoor acrolein is responsible for about 75 percent of non-cancer respiratory health effects attributable to air toxics in the United States, based on the Agency's 2005 NATA (National-Scale Air Toxics Assessment) and acrolein's comparatively potent inhalation reference concentration of 0.02 µg/m3. Assess the association between estimated outdoor acrolein exposure and asthma attack reported by a representative cross-sectional sample of the adult United States population. NATA 2005 chronic outdoor acrolein exposure estimates at the census tract were linked with residences oif adults (≥18 years old) in the NHIS (National Health Interview Survey) 2000 - 2009 (n = 271,348 subjects). A sample-weighted logistic regression model characterized the association between the prevalence of reporting at least one asthma attack in the 12 months prior to survey interview and quintiles of exposure to outdoor acrolein, controlling for potential confounders. In the highest quintile of outdoor acrolein exposure (0.05 - 0.46 µg/m3), there was a marginally significant increase in the asthma attack pOR (prevalence-odds ratio [95% CI] = 1.08 [0.98∶1.19]) relative to the lowest quintile. The highest quintile was also associated with a marginally significant increase in prevalence-odds (1.13 [0.98∶1.29]) in a model limited to never smokers (n = 153,820). Chronic exposure to outdoor acrolein of 0.05 - 0.46 µg/m3 appears to increase the prevalence-odds of having at least one asthma attack in the previous year by 8 percent in a representative cross-sectional sample of the adult United States population.
    Full-text · Article · May 2014 · PLoS ONE
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    • "Interestingly, acrolein was also shown to inhibit NF-kappaB activity in cultured human BAL macrophages, suggesting that acrolein may suppress pulmonary host defense and the ability to mount and resolve a proper inflammatory response (Li et al. 1999; Li and Holian 1998). Overall, data such as those above support that higher dose exposures of acrolein may promote human lung injury, while lower dose exposures may represent risk factors for the development of chronic pulmonary diseases associated with airway inflammatory processes such as asthma and COPD (Bein and Leikauf 2011). "
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    ABSTRACT: The driving environmental factors behind the development of the asthma phenotype remain incompletely studied and understood. Here, we present an overview of inhaled allergic/atopic and mainly nonallergic/nonatopic or toxicant shapers of the asthma phenotype, which are present in both the indoor and outdoor environment around us. The inhaled allergic/atopic factors include fungus, mold, animal dander, cockroach, dust mites, and pollen; these allergic triggers and shapers of the asthma phenotype are considered in the context of their ability to drive the immunologic IgE response and potentially induce interactions between the innate and adaptive immune responses, with special emphasis on the NADPH-dependent reactive oxygen-species-associated mechanism of pollen-associated allergy induction. The inhaled nonallergic/nonatopic, toxicant factors include gaseous and volatile agents, such as sulfur dioxide, ozone, acrolein, and butadiene, as well as particulate agents, such as rubber tire breakdown particles, and diesel exhaust particles. These toxicants are reviewed in terms of their relevant chemical characteristics and hazard potential, ability to induce airway dysfunction, and potential for driving the asthma phenotype. Special emphasis is placed on their interactive nature with other triggers and drivers, with regard to driving the asthma phenotype. Overall, both allergic and nonallergic environmental factors can interact to acutely exacerbate the asthma phenotype; some may also promote its development over prolonged periods of untreated exposure, or possibly indirectly through effects on the genome. Further therapeutic considerations should be given to these environmental factors when determining the best course of personalized medicine for individuals with asthma.
    Full-text · Article · Jan 2014 · Advances in Experimental Medicine and Biology
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