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

Authors

Daniel J. Conklin
Marina V. Malovichko, University of Louisville
Iris Zeller, University of Louisville
Trinath P. Das, University of Louisville
Tatiana V. Krivokhizhina, University of Louisville
Blake H. Lynch, University of Louisville
Pawel Lorkiewicz, University of Louisville
Abhinav Agarwal, University of Louisville
Nalinie Wickramasinghe, University of Louisville
Jasmit Shah, Aga Khan UniversityFollow

Document Type

Article

Department

Internal Medicine (East Africa); Brain and Mind Institute

Abstract

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-1þ cells, CD19þ B-cells, CD4þ T-cells; CD11bþ monocytes) whilst other subsets (eg, CD8þ cells, NK1.1þ cells, Ly6Cþ 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 lowlevel (

Comments

This work was published before the author joined Aga Khan University.

Publication (Name of Journal)

Toxicological Sciences

Recommended Citation

Conklin, D. J., Malovichko, M. V., Zeller, I., Das, T. P., Krivokhizhina, T. V., Lynch, B. H., Lorkiewicz, P., Agarwal, A., Wickramasinghe, N., Shah, J. (2017). Biomarkers of chronic acrolein inhalation exposure in mice: implications for tobacco product-induced toxicity. Toxicological Sciences, 158(2), 263-274.
Available at: https://ecommons.aku.edu/bmi/112