Effects of excessive alcohol drinking on nicotine biotransformation in rats

Alcohol and nicotine (tobacco smoke) are often used together, and taking both addictive substances is associated with an increased risk of certain diseases. It is extremely important to understand the pharmacodynamic and pharmacokinetic mechanisms of the interaction between nicotine and ethanol, which are still not fully understood. The study aimed to evaluate the influence of chronic alcohol consumption on nicotine biotransformation in ethanol-preferring and non-preferring male and female rats. Rats were divided into four groups depending on their alcohol preferences and gender. Nicotine, nornicotine, nicotine N-oxide, cotinine, trans-3'-hydroxycotinine, and cotinine N-oxide in rats plasma were determined by LC–MS/MS after five days of exposure to tobacco smoke. A non-compartmental analysis of nicotine and its metabolites was used for pharmacokinetic parameters calculation. Our experimental results showed that the rate of nicotine elimination depends on gender, regardless of alcohol preferences (significantly slower in females than in males). Mean residence timeof nornicotine, cotinine, and trans-3'-hydroxycotinine were significantly higher in alcohol-preferring male rats than in alcohol preferring female rats. In non-alcohol preferring female rats compared to ethanol-preferring female rats, significantly more nicotine N-oxide (fivefold) and trans-3'-hydroxycotinine (twofold) reached the general circulation unchanged. Drinking ethanol influenced the elimination of nornicotine and cotinine in male rats. Ethanol consumption was identified as a modifier of nicotine pharmacokinetics and this was gender-dependent

The influence of prenatal exposure to tobacco smoke on neonatal body proportions

The objective of this study was to determine neonatal anthropometric indices such as: birth weight, crown-heel length, head and chest circumference and ponderal index , in relation to the maternal smoker status (active and passive smoking). The study included 147 neonates born in 2003-2004 at the Princess Anna Mazowiecka University Hospital in Warsaw admitted to the Neonatal and Intensive Care Department of Warsaw Medical University. Neonates were assigned to one of three groups: babies of mothers who were active smokers, passive smokers and non-smokers based on a questionnaire concerning exposure to tobacco smoke and on the concentration of cotinine in maternal urine. The babies of mothers who were active smokers were born with lower birth weight (p=0.033), lower crown-heel length (p=0.026), lower head circumference (p=0.002) and lower chest circumference (p=0.021) significantly more often than babies of non-smoker mothers. Babies whose mothers were active smokers had an increased risk of lower head circumference or 3, 9 (1, 4-10, 7, CI 95%), and an increased risk of lower chest circumference OR 4, 0 (1, 5-10, 9, CI 95%). The babies of mothers who were passive smokers also had lower anthropometric indices, but the differences were not statistically significant. No effect on ponderal index was observed among the neonates whose mothers were active and passive smokers. Smoking during pregnancy causes symmetrical restriction of intrauterine growth

The impact of intrauterine tobacco exposure on the cerebral mass of the neonate based on the measurement of head circumference

The objective of the study was to assess cerebral mass, based on head circumfer- ence measurements in neonates exposed to tobacco smoke in utero, and to deter- mine the relative proportions of the cerebral and body mass. The study included 147 neonates born in the period 2003–2004 at the Princess Anna Mazowiecka University Hospita land admitted to the Neonatal and Intensive Care Department of the Medical University in Warsaw. Subjects were divided into three groups on the basis of maternal status as active, passive, or nonsmokers determined by materna lurinary cotinine concentration and a questionnaire. Neonates whose mothers were active smokers throughout the whole period of pregnancy had a lower head circumference and in consequence a lower cerebral mass significantly more frequently when compared with those whose mothers were nonsmokers, P=0.002. (Median difference in cerebral mass was 48.27 g.) The risk of lower cerebral mass was 3.9 (1.4–10.8, CI 95%) in the group of neonates whose mothers actively smoked cigarettes during pregnancy. A negative correlation was seen between cerebral mass and maternal urinary cotinine concentration (correlation coefficient r=−23, P=0.006). The ratio of the cerebral to body mass was similar for neonates in all three groups. Active smoking during pregnancy had a negative effect on the cerebral mass of theneonate, however no such effect was observed in neonates whose mothers were passive smokers. The deficiency in cerebral mass increased with greater smoking intensity. Active smoking by the mother during pregnancy inhibits the growth of the brain as well as that of the body mass of the neonate

Localisation of exogenous surfactants in cell membranes in the air-blood barrier : rat model

The use of exogenous surfactants has been introduced into the therapy of patients of different ages. Much better results have been obtained in the treatment of respiratory distress syndrome with surfactants enriched with surfactant proteins. In the following study we used protein-containing surfactants (survanta and curosurf). The aim of the following study was to determine the localisation of artificial surfactants in the lung tissue. Using the Immunogold Technique, biotinylated surfactant proteins were traced in the air-blood barriers. In all lungs the exogenous surfactant was present only in some alveoli. In these parts small areas of atelectasis as well as oedema and transudate accumulation were seen. These changes were less severe after biotinylated curosurf treatment. In electron microscope studies we found surfactant elements in the air-blood barrier and other structures of the alveolar septa. Immunogold studies confirm the presence of biotynylated surfactant in the elements of the air-blood barrier

Localisation of exogenous surfactants in cell membranes in the air-blood barrier: rat model

The use of exogenous surfactants has been introduced into the therapy of patients of different ages. Much better results have been obtained in the treatment of respiratory distress syndrome with surfactants enriched with surfactant proteins. In the following study we used protein-containing surfactants (survanta and curosurf). The aim of the following study was to determine the localisation of artificial surfactants in the lung tissue. Using the Immunogold Technique, biotinylated surfactant proteins were traced in the air-blood barriers. In all lungs the exogenous surfactant was present only in some alveoli. In these parts small areas of atelectasis as well as oedema and transudate accumulation were seen. These changes were less severe after biotinylated curosurf treatment. In electron microscope studies we found surfactant elements in the air-blood barrier and other structures of the alveolar septa. Immunogold studies confirm the presence of biotynylated surfactant in the elements of the air-blood barrier

Influence of tobacco smoke on the pharmacokinetics of citalopram and its enantiomers

The purpose of this study was to evaluate the influence of tobacco smoke on the pharmacokinetics of citalopram (CIT) and desmethylcitalopram (DCIT) and its enantiomers on an animal model. High performance liquid chromatography (HPLC) with a diode array detector (DAD) was used for the identification and quantification of the studied compounds. The HPLC quantification of racemic mixtures of CIT was performed on a C18 column. The limits of detection (LOD) and quantification (LOQ) were: 7 and 10 ng/ml respectively. HPLC separation of citalopram enantiomers (S- and R-CIT) was performed on a Chirobiotic V column. The limits of detection (LOD) and quantification (LOQ) were: 6 and 15 ng/ml for R- and S-CIT respectively. The experiment was carried out on male Wistar rats. The rats were exposed to tobacco smoke for five days (6 hours per day). After the exposure, citalopram was administered in a dose of 10 mg/kg intragastrically. In the control group (non-exposed animals), citalopram was administered in the same way and at an equal dose. The blood of the animals was collected at nine time points. It was found that tobacco smoke exposure inhibits the biotransformation of citalopram. The half-life of the racemic mixture of citalopram after intragastric administration was increased by about 287%. Changes in the pharmacokinetic parameters of S-citalopram (active isomer) show a similar tendency to those of the racemic mixture. The pharmacokinetics of R-citalopram showed no statistically important differences after tobacco smoke exposure. Alterations in the pharmacological parameters of desmethylcitalopram presented an opposite trend to the parent drug. After exposure to tobacco smoke, the induction of metabolism of this compound was observed

Concentrations of Transition Metal Ions in Rat Lungs after Tobacco Smoke Exposure and Treatment with His-Leu Dipeptide

Tobacco smoking is deleterious to the lungs because it exposes them to many toxic substances. These include transition metal ions, such as cadmium. However, there is a lack of information about the influence of endogenous metal-binding peptides, such as His-Leu (HL), on the lung distribution of transition metals in smokers. To address this, we administered HL subcutaneously to rats exposed to tobacco smoke for six weeks, then we measured the concentrations of transition metal ions in the lungs. We found that exposure to tobacco smoke elevates the concentrations of Cd(II) and Cu(II). Administration of the HL peptide, whose elevation is a consequence of angiotensin receptor blocker anti-hypertension therapy, increases the concentration of Fe in the lungs of rats exposed to smoke. These findings suggest that smoking is a risk factor for patients receiving angiotensin receptor blockers to treat hypertension