Advantages and Disadvantages of Electronic Cigarettes.

Despite nearly nine thousand publications on e-cigarettes (EC) in the PubMed database, there is still no consensus in the scientific community and among decision makers regarding the risks and benefits of using these products [...].

E-Liquids from Seven European Countries-Warnings Analysis and Freebase Nicotine Content.

Electronic cigarettes are available in a variety of devices with e-liquids also available in many flavors, and nicotine concentrations, albeit less than 20 mg/mL in Europe. Given the dynamics of these products, it is important to evaluate product content, including labeling, nicotine content versus labeled claim, nicotine form, and other aspects that may help policy decisions and align with the Tobacco Product Directive (TPD). Herein, we performed a study on 86 e-liquids from seven European countries (Croatia, Czech Republic, France, Germany, Italy, Poland, and the United Kingdom) with 34 different liquid brands and 57 different flavors. Nicotine content versus labeled claim, labeling, volume, pH, and nicotine form (i.e., freebase nicotine) were evaluated. From all tested products, eight of them from Germany, Poland, and UK (from 3 to 18 mg/mL), met the ±2% criteria. The ±10% criteria was fulfilled by 50 (58.1%) liquids from all countries. Among 71 liquids which contained nicotine, (one e-liquid labeled as 6 mg/mL had no nicotine level quantified), the amount of freebase nicotine differed from 0 to 97.8%, with a mean value 56.5 ± 35.7. None of the tested liquids had nicotine salt listed in the ingredients. Therefore, a low level of freebase nicotine in some liquids was most likely achieved by added flavorings. All tested liquids presented in this study met the basic requirements of the TPD. There were differences in the scope of information about harmfulness, type of warnings on packaging, attaching leaflets, placing graphic symbols, and discrepancies between the declared and quantified nicotine concentrations.

LC-MS/MS method for simultaneous quantification of dexamethasone and tobramycin in rabbit ocular biofluids.

The complexity of Tobradex® ointment formulation (dexamethasone 0.1 wt% and tobramycin 0.3 wt%) and the high cost of pharmacokinetic (PK) studies in human aqueous humor may prevent generic drug companies from moving forward with a Tobradex®-equivalent product development. The in vitro drug release test would be an alternative approach for differentiating the generic formulations containing both dexamethasone (DEX) and tobramycin (TOB), and the results should be correlated with the in vivo ocular PK studies for further evaluation. To facilitate the in vivo ocular PK studies, a sensitive, rapid and specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) method that can simultaneously quantify both DEX and TOB in rabbit ocular matrices including tear, aqueous humor and cornea was established and validated. The lower limit of quantification (LLOQ) was 1.5 ng/ml for DEX and 3 ng/ml for TOB with good precision and accuracy. Both intra- and inter-batch precisions were within ±15%, and the accuracy for all QCs was within the range of 85-115%. This new method was successfully applied for a pilot pharmacokinetic analysis of DEX and TOB in rabbit tears after topical administration of Tobradex® ointment.

Polyphenols' Cardioprotective Potential: Review of Rat Fibroblasts as Well as Rat and Human Cardiomyocyte Cell Lines Research.

According to the World Health Organization, cardiovascular diseases are responsible for 31% of global deaths. A reduction in mortality can be achieved by promoting a healthy lifestyle, developing prevention strategies, and developing new therapies. Polyphenols are present in food and drinks such as tea, cocoa, fruits, berries, and vegetables. These compounds have strong antioxidative properties, which might have a cardioprotective effect. The aim of this paper is to examine the potential of polyphenols in cardioprotective use based on in vitro human and rat cardiomyocytes as well as fibroblast research. Based on the papers discussed in this review, polyphenols have the potential for cardioprotective use due to their multilevel points of action which include, among others, anti-inflammatory, antioxidant, antithrombotic, and vasodilatory. Polyphenols may have potential use in new and effective preventions or therapies for cardiovascular diseases, yet more clinical studies are needed.

The Time Course of Compensatory Puffing With an Electronic Cigarette: Secondary Analysis of Real-World Puffing Data With High and Low Nicotine Concentration Under Fixed and Adjustable Power Settings.

INTRODUCTION: In a secondary analysis of our published data demonstrating compensatory vaping behavior (increased puff number, puff duration, and device power) with e-cigarettes refilled with low versus high nicotine concentration e-liquid, here we examine 5-day time course over which compensatory behavior occurs under fixed and adjustable power settings. AIMS AND METHODS: Nineteen experienced vapers (37.90 ± 10.66 years, eight females) vaped ad libitum for 5 consecutive days under four counterbalanced conditions (ie, 20 days in total): (1) low nicotine (6 mg/mL)/fixed power (4.0 V/10 W); (2) low nicotine/adjustable power; (3) high nicotine (18 mg/mL)/fixed power; (4) high nicotine/adjustable power (at 1.6 Ohm). Puff number, puff duration, and power settings were recorded by the device. For each day, total daily puffing time was calculated by multiplying daily puff number by mean daily puff duration. RESULTS: A significant day × setting interaction revealed that whilst puffing compensation (daily puffing time) continued to increase over 5 days under fixed power, it remained stable when power settings were adjustable. Separate analysis for puff number and puff duration suggested that the puffing compensatory behavior was largely maintained via longer puff duration. CONCLUSIONS: Under fixed power conditions (4.0 V/10 W), vapers appear to compensate for poor nicotine delivery by taking longer puffs and this compensatory puffing appears to be maintained over time. IMPLICATIONS: Studies in smokers suggest that when switching to lower nicotine levels, compensation for poorer nicotine delivery is transient. Our novel findings suggest that vapers show a different pattern of compensation which is influenced by both nicotine strength and device power settings. When power is fixed (4.0 V; 10 W), compensation (via more intensive puffing) appears prolonged, persisting up to 5 days. Under adjustable settings when power is increased, puffing patterns remain stable over time. Implications of such compensatory behaviors for product safety and user satisfaction need further exploration.

Impact of smoked cannabis on tobacco cigarette smoking intensity and subjective effects: A placebo-controlled, double-blind, within-subjects human laboratory study.

Co-users of cannabis and tobacco frequently use cannabis, then tobacco cigarettes, in a sequential pattern within an occasion, that is, they "chase" smoked cannabis with a tobacco cigarette. The objective of this placebo-controlled, double-blind, within-subjects human laboratory study was to gather preliminary data on how smoking active versus placebo cannabis impacts tobacco cigarette smoking behavior, craving, and subjective effects. Adult daily cannabis and tobacco co-users (N = 9) were randomly assigned to two experimental visit orders (i.e., active cannabis (5.2% THC) first visit and placebo cannabis second visit, or vice versa). Participants smoked one cannabis cigarette, and approximately 30 min later were given a 5-min ad libitum period to smoke one of their own brand of tobacco cigarette. As expected, boost in plasma THC levels and cannabis-related subjective effects differed between active and placebo cannabis conditions. Tobacco cigarette puff topography measures and tobacco craving did not differ between cannabis conditions, but there appeared to be between-participants heterogeneity in cumulative total puff volume. After smoking active versus placebo cannabis, the changes in subjective effects of tobacco smoking after adjusting for pretobacco smoking levels were not significant. Results do not support the notion that immediate effects of smoked cannabis change the behavior of tobacco smoking. The strong overlap between cannabis and tobacco smoking may not be explained by primarily pharmacological factors, but may be driven by more nuanced and complex mechanisms involving pharmacological processes as well as learning factors. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

In vitro anticancer activity of fluphenazine, perphenazine and prochlorperazine. A review.

Drug repositioning is an approach that could accelerate the clinical use of compounds in different diseases. The goal is to take advantage of the fact that approved drugs have been tested on humans and detailed information is available on their pharmacology, toxicity and formulation. It can significantly reduce the costs and time needed to implement necessary therapies on the market. In recent years, phenothiazines are being tested for cancer, viral, bacterial, fungal and other diseases. Most research focuses on chlorpromazine as a model drug in this class, but other drugs such as fluphenazine, perphenazine and prochlorperazine have been proven to inhibit the viability of different cancer cell lines. In this study, we performed an extensive literature search to find and summarize all papers on the chosen phenothiazines and their potential in treating different types of cancerin vitro for further animal/clinical trials. Fluphenazine, perphenazine and prochlorperazine possess anticancer activity towards different types of human cancer. The antitumor activity is mainly mediated by an effect of the drugs on the cell cycle, proliferation or apoptosis. Possible molecular targets of phenothiazine derivatives are the drug's efflux pumps (ABCB1 and P-glycoprotein) and two parallel pathways (AKT and Wnt) regulated by the D2 receptor antagonists. The drugs have the potential to reduce the viability of human cancer cell lines, fragment the DNA, stimulate apoptosis, inhibit cell migration and invasiveness as well as impair the production of reactive oxygen species. In addition, due to the sedative and antiemetic properties antipsychotics can be used as an adjuvant for the treatment of chemotherapy side effects.

Cardioprotective Activity of Selected Polyphenols Based on Epithelial and Aortic Cell Lines. A Review.

Polyphenols have recently gained popularity among the general public as products and diets classified as healthy and containing naturally occurring phenols. Many polyphenolic extracts are available on the market as dietary supplements, functional foods, or cosmetics, taking advantage of clients' desire to live a healthier and longer life. However, due to the difficulty of discovering the in vivo functions of polyphenols, most of the research focuses on in vitro studies. In this review, we focused on the cardioprotective activity of different polyphenols as possible candidates for use in cardiovascular disease therapy and for improving the quality of life of patients. Thus, the studies, which were mainly based on endothelial cells, aortic cells, and some in vivo studies, were analyzed. Based on the reviewed articles, polyphenols have a few points of action, including inhibition of acetylcholinesterase, decrease in reactive oxygen species production and endothelial tube formation, stimulation of acetylcholine-induced endothelium-derived mediator release, and others, which lead to their cardio- and/or vasoprotective effects on endothelial cells. The obtained results suggest positive effects of polyphenols, but more long-term in vivo studies demonstrating effects on mechanism of action, sensitivity, and specificity or efficacy are needed before legal health claims can be made.

Intramuscular atenolol and levetiracetam reduce mortality in a rat model of paraoxon-induced status epilepticus.

Organophosphorus (OP) compounds are chemical threat agents and are irreversible inhibitors of the enzyme acetylcholinesterase that lead to a hypercholinergic response that could include status epilepticus (SE). SE particularly targets the heart and brain and despite existing therapies, it is still associated with significant mortality and morbidity. Here, we investigated the effect of intramuscular (i.m.) adjunct therapy consisting of atenolol (AT) and levetiracetam (LV) when administered after paraoxon (POX)-induced SE. The combination therapy was administered twice daily for 2, 7, or 14 days. POX exposure in rats produced rapid SE onset that was treated with atropine, pralidoxime chloride, and midazolam. Here, AT + LV therapy produced significant reductions in POX SE mortality assessed at 30 days post-SE. AT + LV therapy exhibited muscle pathology inflammation scores that were not significantly different from saline-treated controls. Pharmacokinetic analyses revealed that the i.m. route achieved faster and stabler plasma therapeutic levels for both AT and LV under OP SE conditions compared with oral administrations. Our data provide evidence of the safety and efficacy of i.m. AT + LV therapy for reducing mortality following POX SE.

Antiviral activity of chlorpromazine, fluphenazine, perphenazine, prochlorperazine, and thioridazine towards RNA-viruses. A review.

In 2020 the whole world focused on antivirus drugs towards SARS-CoV-2. Most of the researchers focused on drugs used in other viral infections or malaria. We have not seen such mobilization towards one topic in this century. The whole situation makes clear that progress needs to be made in antiviral drug development. The first step to do it is to characterize the potential antiviral activity of new or already existed drugs on the market. Phenothiazines are antipsychotic agents used previously as antiseptics, anthelminthics, and antimalarials. Up to date, they are tested for a number of other disorders including the broad spectrum of viruses. The goal of this paper was to summarize the current literature on activity toward RNA-viruses of such drugs like chlorpromazine, fluphenazine, perphenazine, prochlorperazine, and thioridazine. We identified 49 papers, where the use of the phenothiazines for 23 viruses from different families were tested. Chlorpromazine, fluphenazine, perphenazine, prochlorperazine, and thioridazine possess anti-viral activity towards different types of viruses. These drugs inhibit clathrin-dependent endocytosis, cell-cell fusion, infection, replication of the virus, decrease viral invasion as well as suppress entry into the host cells. Additionally, since the drugs display activity at nontoxic concentrations they have therapeutic potential for some viruses, still, further research on animal and human subjects are needed in this field to verify cell base research.

Nicotine forms: why and how do they matter in nicotine delivery from electronic cigarettes?

INTRODUCTION: Unregulated e-cigarette devices and their nicotine content have amplified the potential of e-cigarettes as addictive agents. Several e-cigarette-related parameters have been identified altering nicotine's absorption profile, so their potential effects on addiction should be considered. Of these factors, nicotine forms (protonated and free base) play a significant role in the addiction potential yet their impact on nicotine's absorption has been studied with limited research. AREAS COVERED: Current review aims to emphasize on the possible mechanism behind different absorption profiles of nicotine forms considering their physical states (droplet and vapor phase) and the aerosol particle size, their analysis in e-cigarette research and the regulatory attention warranted by them to combat nicotine addiction in the population due to e-cigarettes. EXPERT OPINION: The protonated form of nicotine is being correlated with the smooth sensory effects and high nicotine absorption as compared to free base nicotine. With the introduction of nicotine salts, which yield mostly the protonated form, the youth popularity of e-cigarettes has spiked exponentially. While it is important to control nicotine levels in e-cigarette products, attention should also be given to the nicotine forms present in these products in order to address nicotine addiction in the population.

Daily exposure to formaldehyde and acetaldehyde and potential health risk associated with use of high and low nicotine e-liquid concentrations.

Recent evidence suggests that e-cigarette users tend to change their puffing behaviors when using e-liquids with reduced nicotine concentrations by taking longer and more frequent puffs. Using puffing regimens modelled on puffing topography data from 19 experienced e-cigarette users who switched between 18 and 6 mg/mL e-liquids with and without power adjustments, differences in daily exposure to carbonyl compounds and estimated changes in cancer risk were assessed by production of aerosols generated using a smoking machine and analyzed using gas and liquid chromatography. Significant differences across conditions were found for formaldehyde and acetaldehyde (p < 0.01). Switching from a higher to a lower nicotine concentration was associated with greater exposure regardless of whether power settings were fixed or adjustable which is likely due to increased liquid consumption under lower nicotine concentration settings. Daily exposure for formaldehyde and acetaldehyde was higher for 17/19 participants when using low (6 mg/mL) compared with high (18 mg/mL) nicotine e-liquid concentration when power was fixed. When power adjustments were permitted, formaldehyde and acetaldehyde levels were higher respectively for 16/19 and 14/19 participants with the use of 6 compared with 18 mg/mL nicotine e-liquid.

An Analytical Perspective on Determination of Free Base Nicotine in E-Liquids.

In electronic cigarette users, nicotine delivery to lungs depends on various factors. One of the important factors is e-liquid nicotine concentration. Nicotine concentration in e-liquids ranges from 0 to >50 mg/mL. Furthermore, nicotine exists in protonated and unprotonated ("free base") forms. The two forms are believed to affect the nicotine absorption in body. Therefore, in addition to total nicotine concentration, e-liquids should be characterized for their free base nicotine yield. Two approaches are being used for the determination of free base nicotine in e-liquids. The first is applying a dilution to e-liquids followed by two methods: Henderson-Hasselbalch theory application or a Liquid-Liquid Extraction. The second is the without-dilution approach followed by 1H NMR method. Here, we carried out controlled experiments using five e-liquids of different flavors using these two approaches. In the dilution approach, the Henderson-Hasselbalch method was tested using potentiometric titration. The accuracy was found to be >98% for all five e-liquid samples (n = 3). A Liquid-Liquid Extraction was carried out using toluene or hexane as extraction solvent. The Liquid-Liquid Extraction technique was found to be limited by solvent interactions with flavors. Solvent extractions resulted in flavor dependent inaccuracies in free base nicotine determination (5 to 277% of calculated values). The without-dilution approach was carried out using 1H NMR as described by Duell et al. This approach is proposed to offer an independent and alternative scale. None of the methods have established a strong correlation between pre- and postvaporization free base nicotine yield. Here we present comparative results of two approaches using analytical techniques. Such a comparison would be helpful in establishing a standardized method for free base nicotine determination of e-liquids.

Metal Concentration Assessment in the Urine of Cigarette Smokers Who Switched to Electronic Cigarettes: A Pilot Study.

Background: E-cigarettes (ECs) seem to be a less harmful alternative for conventional cigarettes, however, very little is still known about the exposure to some elements, which are the components of this device and may contaminate the nicotine liquid. The aim of this study is to assess whether e-cigarette users are more exposed to 12 elements detected in aerosol than non-smokers and conventional cigarette smokers, using their concentrations in urine as exposure biomarkers. Methods: A cross-sectional, group-based survey was carried out using 90 volunteers classified into groups of non-smokers, EC-only users, dual EC users-cigarette smokers and cigarette-only smokers. Using inductively coupled plasma mass spectrometry (ICP-MS) and electrothermal atomic absorption spectrometry (ETAAS), Cr, Ni, Co, Ag, In, Mn, Ba, Sr, V, Sb, Cd and Pb levels were measured in spot urine samples. Among the selected groups, a comparison was made using the analysis of covariance and correlations with EC usage pattern were assessed by multiple linear regression. Results: Element concentrations in urine of EC-users were not significantly different from the levels found in non-smokers and smokers. Only in the case of Ba, Ni and Sb was a significant correlation found in relation to some e-cigarette usage patterns. Conclusion: Transfer of the investigated elements to the EC aerosol was not found to be a substantial source of exposure in EC users who quitted smoking.

E-cigarettes and their impact on health: from pharmacology to clinical implications.

Worldwide, cigarette smoking is the major cause of premature mortality and diseases that can be prevented. Given that people continue smoking despite associated health risks, delivering nicotine without combustion should be considered a valuable and much less harmful way to reduce the public health burden caused by smoking. E­cigarettes could play such a role if they were proven to be less harmful than combustible cigarettes. Although the number of clinical trials and human studies assessing the safety of e­cigarettes is limited, numerous in vitro and in vivo studies reported on the potential harmful effects of the aerosol generated from e­cigarettes. This article reviews the results of major clinical trials and laboratory studies with regard to cancer as well as cardiovascular and respiratory risk associated with the use of e­cigarettes. Additionally, it also discusses the potential application of e­cigarettes as smoking cessation tools. Most studies have indicated so far that e­cigarettes are less harmful, but this applies only to smokers who completely switched to e­cigarettes. In the opinion of the authors, good-quality research is crucial to establish the tolerance, safety, efficacy, and harm reduction potential of new technologies. Considering a significant role that physicians and other health providers play in helping smokers, there is an urgent need for evidence­based guidelines and recommendations for clinical practitioners on potential benefits and risks of e­cigarette use.

Author Correction: The Effect of Electronic Cigarette User Modifications and E-liquid Adulteration on the Particle Size Profile of an Aerosolized Product.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Genetically determined metabolism of nicotine and its clinical significance.

Enzymes of the cytochrome P-450 (CYP 450) which belong to the family of oxidase enzymes, are present in cells of all organisms and play a major role in the first phase of xenobiotic metabolism. There are several isoenzymes of CYP 450 that show differences in the speed of metabolism: poor-, extensive- and ultra-rapid. Nicotine undergoes biotransformation in the liver mainly by the CYP2A6 isoform of CYP 450. There are many polymorphic isoforms of CYP2A6 affecting the metabolism of nicotine. There are also several CYP2A6 activity inhibitors and inducers among commonly used drugs. The ability of CYP2A6 isozymes to activate certain procancerogenic substances present in cigarette smoke makes their polymorphism more significant. Moreover, some isoforms may have also influence on the risk of lung cancer development by affecting the enzymatic activation of tobacco-specific nitrosamines. Metabolism of nicotine, mainly through CYP2A6, has also many clinical implications, such as efficacy and safety of the nicotine replacement therapy (NRT) or occurrence of several diseases. In summary, type of the nicotine metabolism may be a potential predictor of the clinical outcomes in patients with cardiovascular disease, addicted to nicotine and in those using NRT. The purpose of this work is to summarize current knowledge on variation in genetically determined metabolism of nicotine and its clinical significance.

The Effect of Electronic Cigarette User Modifications and E-liquid Adulteration on the Particle Size Profile of an Aerosolized Product.

Electronic cigarettes (e-cigarettes) are an alternate nicotine delivery system that generate a condensation aerosol to be inhaled by the user. The size of the droplets formed in the aerosol can vary and contributes to drug deposition and ultimate bioavailability in the lung. The growing popularity of e-cigarette products has caused an increase in internet sources promoting the use of drugs other than nicotine (DOTNs) in e-cigarettes. The purpose of this study was to determine the effect of various e-cigarette and e-liquid modifications, such as coil resistance, battery voltage, and glycol and drug formulation, on the aerosol particle size. E-liquids containing 12 mg/mL nicotine prepared in glycol compositions of 100% propylene glycol (PG), 100% vegetable glycerin (VG), or 50:50 PG:VG were aerosolized at three voltages and three coil resistances. Methamphetamine and methadone e-liquids were prepared at 60 mg/mL in 50:50 PG:VG and all e-liquids were aerosolized onto a 10 stage Micro-Orifice Uniform Deposit Impactor. Glycol deposition correlated with drug deposition, and the majority of particles centered between 0.172-0.5 µm in diameter, representing pulmonary deposition. The 100% PG e-liquid produced the largest aerosol particles and the 100% VG and 50:50 PG:VG e-liquids produced ultra-fine particles <0.3 µm. The presence of ultrafine particles indicates that drugs can be aerosolized and reach the pulmonary alveolar regions, highlighting a potential for abuse and risk of overdose with DOTNs aerosolized in an e-cigarette system.

Exposure to Cadmium and Lead in Cigarette Smokers Who Switched to Electronic Cigarettes.

INTRODUCTION: Electronic cigarettes (ECs) seem to be a less harmful alternative for conventional cigarettes. This study aimed to assess whether the generated aerosols from ECs contain lower amount of cadmium (Cd) and lead (Pb) than cigarette smoke and to detect any changes in exposure to Cd and Pb among cigarette smokers who switched completely or partially to EC. METHODS: EC aerosols and cigarette smoke were generated, and the determination of Cd and Pb in trapped samples and e-liquids was performed by the electrothermal atomic absorption spectrometry method. A cross-sectional, group-based survey was carried out using 156 volunteers classified into groups of nonsmokers, EC-only users, dual EC users-cigarette smokers, and cigarette-only smokers. Using electrothermal atomic absorption spectrometry, blood Cd and Pb levels were measured, and the results were compared by analysis of covariance. RESULTS: Transfer of Cd and Pb to EC aerosol was found to be minimal, although the metals were present in the remaining e-liquid from tanks used for vapor generation. The geometric mean blood Cd concentration adjusted for age and sex was 0.44 (95% confidence interval = 0.37 to 0.52) µg/L in the EC-only users, which was significantly lower than those in the smokers of 1.44 (1.16 to 1.78) and dual users of 1.38 (1.11 to 1.72). The blood Pb geometric mean differed significantly only between nonsmokers of 11.9 (10.6 to 13.3) and smokers of 15.9 (13.6 to 18.6). CONCLUSION: The study revealed that smokers who completely switched to ECs and quit smoking conventional cigarettes may significantly reduce their exposure to Cd and probably Pb. IMPLICATIONS: Switching to EC use is associated with a rapid and substantial decrease in the exposure to carcinogenic Cd. Exposure to Pb is probably also decreased but may be overshadowed by other factors. The study provides empirical data based not only on the analysis of generated aerosol but also on biological indicators of recent exposure-that is, the concentrations of Cd and Pb in blood, indicating EC as a potential harm-reduction device, especially regarding Cd exposure. However, in this case, dual EC use-cigarette smoking provides doubtful benefits.

Mitochondrial functioning abnormalities observed in blood platelets of chronic smoke-exposed guinea pigs - a pilot study.

BACKGROUND: COPD represents a major global health issue, which is often accompanied by cardiovascular diseases. A considerable body of evidence suggests that cardiovascular risk is elevated by the activation of blood platelets, which in turn is exacerbated by inflammation. As reactive oxygen species are believed to be an important factor in platelet metabolism and functioning, the aim of our study was to perform a complex assessment of mitochondrial function in platelets in chronic smoke exposed animals with COPD-like lung lesions. MATERIALS AND METHODS: Eight-week-old, male Dunkin Hartley guinea pigs (the study group) were exposed to the cigarette smoke from commercial unfiltered cigarettes (0.9 mg/cig of nicotine content) or to the air without cigarette smoke (control group), using the Candela Constructions® exposure system. The animals were exposed for 4 hours daily, 5 days a week, with 2×70 mL puff/minute, until signs of dyspnea were observed. The animals were bled, and isolated platelets were used to monitor blood platelet respiration. The mitochondrial respiratory parameters of the platelets were monitored in vitro based on continuous recording of oxygen consumption by high-resolution respirometry. RESULTS: An elevated respiration trend was observed in the LEAK-state (adjusted for number of platelets) in the smoke-exposed animals: 6.75 (5.09) vs 2.53 (1.28) (pmol O2/[s ⋅ 1108 platelets]); bootstrap-boosted P 1α=0.04. The study group also demonstrated lowered respiration in the ET-state (normalized for protein content): 12.31 (4.84) vs 16.48 (1.72) (pmol O2/[s ⋅ mg of protein]); bootstrap-boosted P 1α=0.049. CONCLUSION: Our results suggest increased proton and electron leak and decreased electron transfer system capacity in platelets from chronic smoke-exposed animals. These observations may also indicate that platelets play an important role in the pathobiology of COPD and its comorbidities and may serve as a background for possible therapeutic targeting. However, these preliminary outcomes should be further validated in studies based on larger samples.