Abstract 19738: Biomarkers of Exposures and Cardiovascular Toxicity of Smokeless Tobacco Products
Eight million people in the United States use smokeless tobacco products (ST). Epidemiological studies on ST and cardiovascular disease (CVD) are contradictory and non-conclusive. While some studies observed that ST causes hyperlipidemia and increases the risk for myocardial infarction and stroke mortality others did not find any association between ST use and CVD. We examined the effect of chronic exposure to ST (in C57BL/6 mice exposed to snuff or snus containing 100 mg/L nicotine in drinking water for 4, 12 and 24 weeks; n=30/group) on surrogate markers of endothelial damage, insulin resistance, thrombosis and inflammation. Levels of total nicotine and its metabolites cotinine and 3,hydroxy cotinine in the plasma of ST fed mice (~ 25-40 μg/ml) mice were comparable with blood nicotine levels in smokers/ST users. Urinary metabolites of formaldehyde, acetaldehyde, acrolein and crotonaldehyde in ST exposed mice were comparable with water-fed controls. Exposure to ST for 4 or 12 weeks did not affect the levels of circulating endothelial progenitor cells (EPCs) but 24 four weeks of exposure to reference snus, Camel snus (most common commercial snus), reference snuff and Copenhagen snuff (most common commercial snuff) decreased the levels of circulating EPCs by 45-55% (P<0.05). Plasma levels of soluble E-Selectin and ICAM-1 in ST exposed mice were comparable with controls at all time points. Exposure to all the ST products for 4, 12 and 24 weeks decreased the levels of circulating leukocytes (30-60%; P<0.05), B-cells (50-60%; P<0.05), CD4+T-cells (25-40%; P<0.05) and monocytes (50-60%; P<0.05). Twelve and twenty four weeks of exposure to all the STs also decreased CD8+ T-cells (25-35%; P<0.05) in the blood. Effect of ST on circulating EPCs and immune cells were recapitulated by oral nicotine (100 mg/L in drinking) at all time points (P<0.05). Neither ST nor nicotine affected systemic insulin resistance; platelet leukocytes adduct formation in situ; or plasma levels of platelet factor 4 (PF4), fibrinogen and cholesterol. Collectively, these data suggest circulating EPCs and immune cells are sensitive and robust biomarkers of ST-induced endothelial injury and immune suppression, and these effects, at least in parts, are mediated by nicotine levels in ST.
Author Disclosures: M.V. Malovichko: None. I. Zeller: None. A. Agarwal: None. S.D. Sithu: None. T.V. Krivokhizhina: None. N.S. Wickramasinghe: None. M.G. Winner: None. M.E. Smith: None. J.P. McCracken: None. A. Bhatnagar: None. D.J. Conklin: None. S. Srivastava: None.
- © 2016 by American Heart Association, Inc.