Biomarkers of chronic acrolein inhalation exposure in mice: Implications for tobacco product-induced toxicity

Daniel J. Conklin, Marina V. Malovichko, Iris Zeller, Trinath P. Das, Tatiana V. Krivokhizhina, Blake H. Lynch, Pawel Lorkiewicz, Abhinav Agarwal, Nalinie Wickramasinghe, Petra Haberzettl, Srinivas D. Sithu, Jasmit Shah, Timothy E. O'Toole, Shesh N. Rai, Aruni Bhatnagar, Sanjay Srivastava

Research output: Contribution to journalArticlepeer-review

35 Citations (Scopus)


Exposure to tobacco smoke, which contains several harmful and potentially harmful constituents such as acrolein increases cardiovascular disease (CVD) risk. Although high acrolein levels induce pervasive cardiovascular injury, the effects of low-level exposure remain unknown and sensitive biomarkers of acrolein toxicity have not been identified. Identification of such biomarkers is essential to assess the toxicity of acrolein present at low levels in the ambient air or in new tobacco products such as e-cigarettes. Hence, we examined the systemic effects of chronic (12 weeks) acrolein exposure at concentrations similar to those found in tobacco smoke (0.5 or 1 ppm). Acrolein exposure in mice led to a 2-to 3-fold increase in its urinary metabolite 3-hydroxypropyl mercapturic acid (3-HPMA) with an attendant increase in pulmonary levels of the acrolein-metabolizing enzymes, glutathione S-transferase P and aldose reductase, as well as several Nrf2-regulated antioxidant proteins. Markers of pulmonary endoplasmic reticulum stress and inflammation were unchanged. Exposure to acrolein suppressed circulating levels of endothelial progenitor cells (EPCs) and specific leukocyte subsets (eg, GR-1+ cells, CD19+ B-cells, CD4+ T-cells; CD11b+ monocytes) whilst other subsets (eg, CD8+ cells, NK1.1+ cells, Ly6C+ monocytes) were unchanged. Chronic acrolein exposure did not affect systemic glucose tolerance, platelet-leukocyte aggregates or microparticles in blood. These findings suggest that circulating levels of EPCs and specific leukocyte populations are sensitive biomarkers of inhaled acrolein injury and that low-level (<0.5 ppm) acrolein exposure (eg, in secondhand smoke, vehicle exhaust, e-cigarettes) could increase CVD risk by diminishing endothelium repair or by suppressing immune cells or both.

Original languageEnglish
Article numberkfx095
Pages (from-to)263-274
Number of pages12
JournalToxicological Sciences
Issue number2
Publication statusPublished - 1 Aug 2017
Externally publishedYes


  • Aldehydes
  • Cardiovascular disease
  • Endothelial progenitor cells
  • Oxidative stress
  • Pulmonary injury
  • Tobacco


Dive into the research topics of 'Biomarkers of chronic acrolein inhalation exposure in mice: Implications for tobacco product-induced toxicity'. Together they form a unique fingerprint.

Cite this