Effects of electronic cigarette flavorants on human platelet aggregation ex vivo. (2022)

• Record Type: Journal Article
• Authors: Richardson, Andre; Krivokhizhina, Tatiana; Lorkiewicz, Pawel; D'Souza, Stanley; Bhatnagar, Aruni; Srivastava, Sanjay; Conklin, Daniel J.
• Is Part Of: Toxicology reports. Volume 9(2022)
• Page Start: 814
• Page End: 820
• Publication Date: 2022
• Subjects: AA arachidonic acid -- ADP adenosine diphosphate -- CVD cardiovascular disease -- E-cig electronic cigarette -- ENDS, electronic nicotine delivery systems -- GRAS generally regarded as safe -- NO nitric oxide -- P1, phase 1 aggregation -- P2, phase 2 aggregation -- PAF platelet activating factor -- PG propylene glycol -- PPP, platelet-poor plasma -- PRP, platelet-rich plasma -- ROS reactive oxygen species -- TxA2 thromboxane A2 -- VG vegetable glycerol; Electronic cigarettes -- Electronic nicotine delivery systems -- Eugenol -- Flavorants -- Thrombosis -- Tobacco; Toxicology -- Periodicals; Clinical toxicology -- Periodicals; Drug-Related Side Effects and Adverse Reactions; Hazardous Substances; Poisoning; Toxicology; Electronic journals; Periodicals; Periodicals; 571.9505
• DOI: 10.1016/j.toxrep.2022.04.003
• Languages: English
• ISSNs: 2214-7500

Abstract

Abstract: Because little is known about the effects of individual flavorants in electronic cigarette (e-cig) fluids on human platelet aggregation, we tested for the direct effects of 15 common e-cig flavorants on adenosine diphosphate (ADP)-induced human platelet aggregation ex vivo . To better understand a potential mechanism of action of flavorants, we quantified 2 phases of aggregation. Human platelet-rich plasma (PRP) was obtained from whole blood of healthy volunteers and used in a platelet aggregometry assay. PRP was incubated with 1 of 15 different flavorant compounds (e.g., benzyl alcohol, eugenol, citronellol, menthol, menthone, diacetyl, maltol, limonene, methylbutyric acid, isoamyl acetate, acetylpyridine, eucalyptol, 2, 5-dimethylpyrazine, cinnamaldehyde, and vanillin) at 100 µM for 5 min at 37 °C prior to addition of ADP (10 µM). Subsequent ADP-induced platelet aggregation was tracked for 5 min using an aggregometer. Aggregation curves were analyzed for flavorant-induced effects on total (%) aggregation, Phase 1 and Phase 2 components, and compared with their ADP-only control via One-Way ANOVA. Notably, eugenol significantly inhibited total aggregation; an effect due solely to inhibition of Phase 2. No other flavor tested had any effect on total or phase-specific ADP-induced platelet aggregation. These results indicate that parent flavorant compounds commonly found in e-cig liquids neither activate nor inhibit ADP-induced human platelet aggregation. However, as flavorants are chemically altered during heating of e-cig, thermally-derived products of flavorants (e.g., flavor acetals) also will need to be tested for effects on platelet activation. Graphical Abstract: ga1 Highlights: Fifteen common flavorants used in electronic cigarettes were tested for toxicity in isolated human platelets. Despite using a relatively high concentration of flavorants [100 μM], 14 of 15 flavorants had no effect on ADP-induced aggregation. Eugenol induced concentration dependent inhibition of ADP-induced platelet aggregation Future studies of platelet toxicity of heated flavorants, flavorant metabolites, and flavorant acetals will benefit from these baseline data.