Effects of nicotine, its metabolites and tobacco extracts on human platelet function in vitro

• Published in: Toxicology in vitro 2013-03, Vol.27 (2), p.932-938
• Main Authors: Ljungberg, Liza U., Persson, Karin, Eriksson, Andreas C., Green, Henrik, Whiss, Per A.
• Format: Article
• Language: English
• Subjects: Blood Platelets - drug effects; Blood Platelets - physiology; Cells, Cultured; Cigarette smoke; Cotinine - analogs & derivatives; Cotinine - toxicity; Humans; MEDICIN; MEDICINE; Moist tobacco; Nicotine - analysis; Nicotine - toxicity; Nicotine metabolite; Plant Extracts - chemistry; Plant Extracts - toxicity; Platelet adhesion; Platelet aggregation; Platelet Aggregation - drug effects; Snuff; Tobacco Products
• ISSN: 0887-2333; 1879-3177; 1879-3177
• DOI: 10.1016/j.tiv.2013.01.004

► Tobacco extracts inhibit platelet adhesion to proteins surfaces. ► This effect is independent of nitric oxide and a platelet nicotine receptor. ► Nicotine and nicotine metabolites have limited effect on platelet activity in vitro. Cigarette smoking is a leading cause of cardiovascular disease. The cardiovascular effects of smoking are probably multifactorial, including effects on platelets. Previous reports investigating the effects of nicotine and tobacco on platelet function are inconsistent. The present study investigated in vitro effects of nicotine, its major metabolites, tobacco extracts and extract of tobacco-free snuff on human platelets. None of the metabolites cotinine, cotinine-N-oxide, nicotine-1′-N-oxide or trans-3′-hydroxycotinine (0.1–10μM) affected platelet aggregation or P-selectin expression. Nicotine (10μM) weakly increased platelet aggregation, whereas trans-3′-hydroxycotinine (0.1μM) and nicotine-1′-N-oxide (1–10μM) weakly inhibited adhesion to fibrinogen. To elucidate the influence of other tobacco compounds, we investigated the impact of moist tobacco and smoke extracts on platelet function. Filtered extracts of oral snuff, cigarette smoke and tobacco free snuff inhibited platelet adhesion concentration-dependently. The inhibitory effects of tobacco extracts on platelet adhesion were independent of nicotine content and the nitric-oxide-pathway and not mediated through a platelet-nicotine-receptor. Taken together, tobacco extracts inhibit platelet activation during short-term in vitro challenge. As only limited effects of nicotine and nicotine metabolites were seen, the tobacco-induced platelet inhibition are likely induced by other compounds present in tobacco and tobacco free snuff.