Systemic Toxicity of Smokeless Tobacco Products in Mice.

ABSTRACT:

Introduction

Smokeless tobacco products such as snuff and snus are used worldwide. However, little is known about the systemic and cardiovascular toxicity of smokeless tobacco exposure.

Methods

Biomarkers of endothelial activation and injury, immune functions, platelet activation and insulin resistance were measured in 8-week old male C57BL/6 mice exposed to commercial snuff, CRP-2 reference snuff, commercial snus, CRP-1 reference snus, and nicotine in drinking water (100 µg/mL) for 4, 12, and 24 weeks.

Results

Twenty-four weeks of exposure to smokeless tobacco products or nicotine significantly decreased the levels of circulating Flk+/Sca+ endothelial progenitor cells. Twelve and 24 weeks of exposure to all the smokeless tobacco products and nicotine significantly decreased the levels of circulating CD19+ B cells, CD4+ T cells, CD8+ T cells, and CD11b+ monocytes, whereas 4 weeks of exposure to Camel snus and Copenhagen snuff significantly depleted the levels of peripheral blood CD19+ B cells and CD11b+ monocytes. Twenty-four weeks of exposure to smokeless tobacco products or nicotine significantly decreased plasma IFN? levels. However, plasma TNF? levels were significantly increased in mice exposed to Copenhagen snuff or nicotine for 24 weeks. This was accompanied by a five to sevenfold increase in the hepatic expression of TNF?. Neither smokeless products nor nicotine affected plasma lipoproteins, platelet activation, or systemic insulin sensitivity.

Conclusions

Chronic exposure to snuff and snus suppresses circulating levels of EPCs, endothelial microparticles and immune cells, but increases plasma TNF-? levels. These effects of smokeless tobacco products are attributable, at least in part, to nicotine.

Implications

Exposure to smokeless tobacco products results in the depletion of endothelial progenitor cells, which may impair the endothelium repair. Suppression of the circulating levels of immune cells upon exposure to smokeless tobacco products may increase the susceptibility to secondary infection. Increased formation of proinflammatory cytokines such as TNF? by nicotine or Copenhagen snuff may lead to vascular inflammation and thereby exacerbate atherogenesis.

SUBMITTER: Malovichko MV 

PROVIDER: S-EPMC6329408 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature