Maksymilian Kulza

Exposure to alcohol and tobacco smoke causes oxidative stress in rats

BACKGROUND Tobacco smoking and alcohol abuse causes oxidative stress in humans and underlay numerous chronic degenerative diseases. Liver is the main organ exposed to alcohol toxic metabolites, whereas tobacco smoke is chiefly harmful to the lungs. METHODS The aim of the current study was the assessment and comparison of selected oxidative stress markers, reduced glutatione (GSH), glutathione S-transferase (GST), superoxide dismutase (SOD), catalase, nitrites and protein nitrosylation and DNA damage in the livers and in the lungs of alcohol-addicted rats exposed to tobacco smoke alone or in combination with a single dose of ethanol. RESULTS The highest levels of GSH were measured in the liver of smoke only exposed animals and in the lungs of rats exposed to smoke and alcohol. In the liver of animals treated with a single dose of alcohol or with smoke and alcohol, GST was significantly higher than in the group exposed to smoke only. SOD and catalase showed the highest activities in the livers of rats receiving a single dose of alcohol. High concentration of nitrites was observed in the lungs of animals treated with smoke and alcohol in combination, which corresponded to elevated protein nitrosylation in this group, whereas in the livers of these animals relatively low level of nitrites was accompanied with the lowest concentration of nitrosylated proteins. In the liver of alcohol only treated rats the highest nitrites corresponded to the highest protein nitrosylation. In the lungs of all treatment groups the range of DNA damage was higher, than the respective values in the livers. Although alcohol is not considered a specific toxicant to the lungs it was found to cause oxidative stress in this organ. CONCLUSIONS The obtained results suggest that in the ethanol-addicted rats combined exposure to smoke and alcohol differentially modulate endogenous antioxidant defense system and reactions to oxidative stress.

Exposure to ethanol and tobacco smoke in relation to level of PCNA antigen expression in pancreatic and hepatic rat cells

BACKGROUND Previous results proved that simultaneous effect of tobacco smoke constituents and alcohol consumption may change toxicity of these substances and have a greater effect on hepatic and pancreatic disease and cancer risk. The aim of this study was to investigate hepatocyte and pancreatic cells regeneration after tobacco and/or ethanol treatment. METHODS In the study, four groups of rats were used - alcohol non-addicted and addicted male and female rats. The animals from each group were exposed to tobacco smoke, to ethanol or tobacco smoke and ethanol. After the exposure, pancreas and liver were collected at two time-points--5 and 24 h. Biochemical methods were used to measure concentration of ethanol and cotinine in blood and plasma. Additionally, proliferating cell nuclear antigen labeling index (PCNA-LI), an S-phase marker was assessed by immunohistochemical staining and morphometric method. RESULTS Our experimental results showed that the exposure of rats to tobacco smoke does not have influence on ethanol concentration in blood of non-addicted (male, female) and addicted (male and female) animals. The results also proved that alcohol addiction did not influence nicotine metabolism in all animals exposed to tobacco smoke. Morphological studies of tissues display significant damage in liver of addicted males, including fatty degradation, fibrosis and slight inflammatory infiltrate. Immunohistochemical studies revealed at first, significant increase of PCNA-LI and, thus, increased cell proliferation activity and damage in tissues were observed in hepatic and pancreatic cells of addicted males when compared with non-addicted males. Secondly, comparison between addicted males and addicted females revealed that PCNA-LI in females is significantly lower, both in hepatic and pancreatic tissues. And finally, animals exposed only to ethanol and to tobacco smoke plus ethanol were characterized by higher percentage of PCNA positive cells in relation to animals exposed only to tobacco smoke. CONCLUSION From the preliminary study one can conclude that the influence of ethanol and simultaneous influence of ethanol and tobacco smoke impairs liver and pancreatic functions to a greater degree than tobacco abuse.

Implications of the alpha dispersion for studies on interaction of tobacco smoke--corneal tissue.

In this work, we have carried out a dielectric study to determine the effect of tobacco smoke on the rat corneal function. Measurements were performed over the frequency range of 500 Hz-100 kHz in air and at the temperature of 35°C. The frequency dependencies of the loss tangent for both healthy and smoky cornea exhibit two peaks with different width occurring as a narrow at 2 kHz and a broad at around 16 kHz. The distribution parameter α at 2 kHz has a value of about 0.3, which increases to 0.6 at 16 kHz. The magnitude of the permittivity decrement at 2 and 16 kHz is about two and four times higher, respectively, for the smoky cornea than that for the healthy one. These dielectric studies indicate that the present method is useful in detection of the effect of tobacco smoke exposure on the corneal behavior.

Intravenous and oral suicidal e-liquid poisonings with confirmed nicotine and cotinine concentrations

The increasing availability of e-cigarettes is a potential toxicological concern. E-cigarettes appeared on the Polish market in 2006, and since 2009 they have been widely available with a new source of nicotine, the so-called e-liquid. In this paper two cases of suicidal oral and intravenous poisonings with the e-liquid are described. The clinical courses of these poisonings are presented. Nicotine and cotinine concentrations in the patients blood were determined using high performance liquid chromatography with diode array detection. In the course of intoxication patient No. 1, classic symptoms of acute nicotine poisoning without convulsions were observed. Nicotine and cotinine concentrations measured in serum were 0.096 and 4.4mg/L, respectively. The case of patient No. 2, admission with no typical symptoms of nicotine poisoning was identified, except unconsciousness and slow respiration. Nicotine and cotinine concentrations in the serum at the time of No. 2 admissions were determined to be 0.8 and 1.3mg/L, respectively. With the increasing number of e-liquid poisonings cases, it should be aware that these products can be a readily available source of poison.

Diabetes mellitus effect on rat corneal dielectric properties

In the course of the study, we carried out a dielectric examination to determine the effect of diabetes mellitus on the rat corneal function. Measurements were performed over the frequency range of 500 Hz-100 kHz in air and at the temperatures from 25 to 150°C. The frequency dependencies of the loss tangent for the healthy and the diabetic cornea exhibit two peaks at 2 kHz and 16 kHz in the α-dispersion region. The amplitude of these both peaks is smaller for the diabetic cornea than that for the healthy one. The temperature dependencies of the loss tangent for the healthy and the diabetic cornea reveal β-relaxation in the range of 30-70°C and 50-90°C, respectively. The present study exhibits that the dielectric spectroscopy is useful in detection of the effect of diabetes mellitus on the corneal molecular behavior.

How to combine non-compartmental analysis with the population pharmacokinetics? A study of tobacco smoke's influence on the bioavailability of racemic citalopram in rats.

BACKGROUND Citalopram (CIT) is an antidepressant drug from the group of selective serotonin reuptake inhibitors in which it is the most potent selective inhibitor of serotonin uptake currently available. Patients treated with CIT are often heavy cigarette smokers. Individual pharmacokinetic parameters cannot be directly estimated if full pharmacokinetic profiles are not available for each subject. Sparse sampling is common to experiments using small animals, such as the case that our study is concerned with. METHODS The aim of the study was to demonstrate how the two (non-compartmental analysis (NCA) and nonlinear mixed-effect (NLME)) approaches, used simultaneously, can help overcome specific limitations of these separate methods whilst at the same time preserve their respective benefits. RESULTS Despite the ultra-sparse design, the NLME approach enabled us to develop a pharmacostatistic model with the required covariate--exposition to the tobacco smoke. CONCLUSIONS A tobacco smoke slows down the absorption of the CIT and at the same time makes it more effective. The consistency of results obtained both with NCA and NLME decreased the risk of model misspecification and increased confidence in the final conclusions. Combining NLME with NCA may therefore be recommended for investigating pharmacokinetic properties of the drug in the sparse designs.