Wpływ melatoniny na aktywność peroksydazy glutationu w surowicy i erytrocytach po iniekcji adriamycyny u szczurów nietkniętych i poddanych pinealektomii

Introduction: Adriamycin (ADR) is a potent chemotherapeutic agent, effective in the treatment of leukaemias, lymphomas and many solid tumours. However, its clinical usage is often limited by cardiotoxicity, induced by oxygen radical damage of the membrane lipids. Melatonin (MEL) is a well-known antioxidant. It has been shown that MEL can scavenge free radicals, both directly and indirectly, stimulating the activity of antioxidative enzymes such as glutathione peroxidase (GSH-Px). The aim of the study: The aim of the study was to examine the effect of MEL on serum and erythrocyte GSH-Px activity after ADR in normal and pinealectomised rats. Material and methods: Wistar rats were divided into the three groups: control animals (Intact), sham-operated (Sham-PX) and pinealectomised (Px). Each of the groups was divided into four subgroups, injected with: 1 - saline, 2 - MEL, 3 - ADR and 4 - ADR + MEL. ADR was administered 2 months after Px as a single dose (15 mg/kg, i.p.) 1 hour after the fourth melatonin injection. Melatonin (5 mg/kg, i.p.) was administered for 4 days before and 2 days after ADR. After 6 days of treatment, the rats were killed by decapitation. Their blood was collected for measurements. Results: In serum GSH-Px activity decreased in all the groups after ADR. Pinealectomy decreased the activity of the enzyme in all the groups of animals examined. In erythrocytes GSH-Px decreased after ADR in the Px-animals. The effect of pinealectomy on erythrocyte GSH-Px activity was not as strongly expressed as serum GSH-Px activity. MEL did not change GSH-Px activity after ADR. Conclusion: Melatonin, in pharmacological concentrations, did not influence the activity of GSH-Px, either in normal or in pinealectomised rats after ADR. A deficiency of endogenous melatonin production may inhibit GSH-Px activity.Wstęp: Adriamycyna (ADR, adriamycin) jest lekiem przeciwnowotworowym wykorzystywanym w leczeniu białaczek, chłoniaków czy guzów litych. Jej efekt leczenia jest ograniczony ze względu na kardiotoksyczność indukowaną produkcją wolnych rodników, które uszkadzają błony lipidowe. Melatonina (MEL, melatonin) jest znanym antyoksydantem. Wykazano, że neutralizuje wolne rodniki w sposób bezpośredni lub pośredni, stymulując enzymy antyoksydacyjne, w tym peroksydazę glutationu (GSH-Px, glutathione peroxidase). Cel: Celem badania było zbadanie efektu melatoniny na aktywność GSH-Px w surowicy i erytrocytach po adriamycynie u zwierząt nietkniętych i po usunięciu szyszynki. Materiał i metody: Szczury samce szczepu Wistar podzielono na 3 grupy: grupę kontrolną (Intact - szczury nietknięte), po operacji pozornej (Sham-Px) i po usunięciu szyszynki (Px). Każdą grupę podzielono na 4 podgrupy, w których podano injekcje: 1 - soli fizjologicznej, 2 - MEL, 3 - ADR i 4 - ADR + MEL. Adriamycynę podano 2 miesiące po Px w dawce jednorazowej (15 mg/kg mc.), 1 godzinę przed czwartym podaniem MEL. Melatoninę podawano przez 4 dni przed Px i przez 2 dni po ADR w dawce 5 mg/kg mc. Po 6 dniach leczenia zwierzęta zabito przez dekapitację, a krew zamrożono do momentu pomiarów. Wyniki: Aktywność PSH-Px w surowicy obniżyła się po ADR we wszystkich badanych grupach. Po usunięciu szyszynki aktywność GSHPx w surowicy zmniejszyła się w grupach poddanych injekcjom. Aktywność GSH-Px w erytrocytach obniżyła się po ADR u zwierząt poddanych Px. Zmiany aktywności GSH-Px w eytrocytach po usunięciu szyszynki były słabiej wyrażone w porównaniu z aktywnością GSH-Px w surowicy. Melatonina nie zmieniła aktywności peroksydaz po ADR. Wnioski: Melatonina w dawce farmakologicznej nie wpłynęła na aktywność peroksydaz zarówno u zwierząt nietkniętych, jak i po usunięciu szyszynki. Deficyt endogennej produkcji melatoniny może odgrywać rolę w hamowaniu aktywności peroksydaz

Mental Health, Well-Being, and Psychological Flexibility in the Stressful Times of the COVID-19 Pandemic

This study investigated the relationships between selected emotional aspects of mental ill-health (depression, anxiety, and stress, DASS) and mental well-health (well-being) experienced during the COVID-19 pandemic. The theoretical model of the study was based on Martin Seligman’s positive psychology and PERMA theory and Paul Wong’s Existential Positive Psychology 2.0 Theory, which postulates that negative experiences contribute to well-being and personal growth. The static approach was complemented by exploring the mediating role of psychological flexibility (defined as acceptance and action in the current situation) in the relationship between negative emotions and well-being. The data were collected during the initial phase of the COVID-19 pandemic from 277 participants (221 women), aged M = 33.83, SD = 12.77. The results confirmed that negative emotions correlated negatively with various domains of well-being (PERM), except for accomplishment (completing tasks and fulfill daily responsibilities). Moreover, negative emotions were related to the general well-being through psychological flexibility in that higher depression, anxiety, and stress were associated with lower psychological flexibility, which decreased general well-being. Finally, negative emotions were shown to be beneficial, having an adaptive effect that allows individuals to maintain their ability to cope with the situation, reach goals, and fulfill daily duties and responsibilities despite critical, stressful situation (like the COVID-19 pandemic) that limit their psychological flexibility. This observation confirmed the positive potential of negative aspects of life postulated within Existential Positive Psychology

Developmental toxicity of N-methylaniline following prenatal oral administration in rats

Objectives: The objective of the study was to assess prenatal toxicity of N-methylaniline (NMA) administered by gavage to pregnant female rats. Material and Methods: Pregnant female rats were administered N-methylaniline in corn oil by gavage at daily doses of 0.8 mg/kg of body weight (b.w.), 4 mg/kg b.w., 20 mg/kg b.w. and 100 mg/kg b.w. from implantation (the 5th day post mating) to the day prior to the scheduled caesarean section (the 20th day of pregnancy). General behavior, body weight, food and water consumption, hematological, biochemical analyses and pathomorphological changes of the dams were recorded. Results: All the females survived until the end of the study. The test substance was toxic to pregnant females, even at the lowest of the used doses, i.e., 0.8 mg/kg b.w./day. Lower weight gain during pregnancy and significantly higher NMA-dose-dependent absolute weight of the organs were noted in the exposed females. The females from the groups exposed at doses of 20 mg/kg b.w./day and 100 mg/kg b.w./day developed anemia and showed higher concentrations of free thyroxine (FT3) and free triiodothyronine (FT4) thyroid hormones. Total protein concentration exhibited an increase in all the exposed groups of females. In the prenatal toxicity study, administration of N-methylaniline throughout the embryonic and fetal periods produced embryotoxic effects at doses ranging 4–100 mg/kg b.w./day. Conclusions: Considering the data obtained in this study, it is reasonable to assume that N-methylaniline administered orally to pregnant rats is toxic for mothers even at a low dose of 0.8 mg/kg b.w./day. However, this dose was not associated with any significant effects to their offspring. This prenatal exposure level may be considered as no-observed-adverse-effect level (NOAEL) for the progeny and a dose of 4 mg/kg b.w./day as the lowest-observed-adverse-effect level (LOAEL) for the progeny

urinary metabolomics study of workers exposed to hexavalent chromium

Exposure to hexavalent chromium Cr(VI) may occur in several occupational activities, placing workers in many industries at risk for potential related health outcomes. Untargeted metabolomics was applied to investigate changes in metabolic pathways in response to Cr(VI) exposure. We obtained our data from a study population of 220 male workers with exposure to Cr(VI) and 102 male controls from Belgium, Finland, Poland, Portugal and the Netherlands within the HBM4EU Chromates Study. Urinary metabolite profiles were determined using liquid chromatography mass spectrometry, and differences between post-shift exposed workers and controls were analyzed using principal component analysis. Based on the first two principal components, we observed clustering by industrial chromate application, such as welding, chrome plating, and surface treatment, distinct from controls and not explained by smoking status or alcohol use. The changes in the abundancy of excreted metabolites observed in workers reflect fatty acid and monoamine neurotransmitter metabolism, oxidative modifications of amino acid residues, the excessive formation of abnormal amino acid metabolites and changes in steroid and thyrotropin-releasing hormones. The observed responses could also have resulted from work-related factors other than Cr(VI). Further targeted metabolomics studies are needed to better understand the observed modifications and further explore the suitability of urinary metabolites as early indicators of adverse effects associated with exposure to Cr(VI).publishersversionpublishe

Toxic effect in the lungs of rats after inhalation exposure to benzalkonium chloride

Background: Benzalkonium chloride (BAC) is a quaternary ammonium compound (QAC) toxic to microorganisms. Inhalation is one of the major possible routes of human exposure to BAC. Materials and Methods: Experiments were performed on female Wistar rats. The rats were exposed to aerosol of BAC water solution at the target concentration of 0 (control group) and 35 mg/m3 for 5 days (6 h/day) and, after a 2-week interval, the animals were challenged (day 21) with BAC aerosol at the target concentration of 0 (control group) and 35 mg/m3 for 6 h. Results: Compared to the controls, the animals exposed to BAC aerosol were characterized by lower food intake and their body weight was significantly smaller. As regards BAC-exposed group, a significant increase was noted in relative lung mass, total protein concentration, and MIP-2 in BALF both directly after the termination of the exposure and 18 h afterwards. Significantly higher IL-6 and IgE concentrations in BALF and a decrease in the CC16 concentration in BALF were found in the exposed group immediately after the exposure. The leukocyte count in BALF was significantly higher in the animals exposed to BAC aerosol compared to the controls. In the lungs of rats exposed to BAC the following effects were observed: minimal perivascular, interstitial edema, focal aggregates of alveolar macrophages, interstitial mononuclear cell infiltrations, thickened alveolar septa and marginal lipoproteinosis. Conclusion: Inhalation of BAC induced a strong inflammatory response and a damage to the blood-air barrier. Reduced concentrations of CC16, which is an immunosuppressive and anti-inflammatory protein, in combination with increased IgE concentrations in BALF may be indicative of the immuno-inflammatory response in the animals exposed to BAC aerosol by inhalation. Histopathological examinations of tissue samples from the BAC-exposed rats revealed a number of pathological changes found only in the lungs

The distribution and excretion of 1-Methylnaphthalene in rats exposed to 1-Methylnaphthalene by inhalation

Objectives 1-Methylnaphthalene (1-MN) is a constituent of polycyclic aromatic hydrocarbons, the chemicals that have become ubiquitous in the environment as result of natural and industrial process. This paper reports a study on the distribution and excretion of 1-MN in rats after single and repeated inhalation exposure to 1-MN vapor. Material and Methods Male Wistar rats were exposed to 1-MN vapor at nominal concentrations of 50 mg/m 3 or 200 mg/m 3 in the dynamic inhalation chambers (TSE Systems Head Nose Only Exposure) for 6 h (single exposure) or 5 days (6 h/day, repeated exposure). Blood, urine and tissue samples were collected during and after the exposure. Blood, urine and tissue concentrations of 1-MN were estimated by gas chromatography using the headspace technique. Results The elimination of 1-MN from blood followed an open 2-compartment model. The concentration in rat tissues was dependent on the magnitude and time of exposure. After repeated exposure, the concentration 1-MN in tissue decreased in comparison to single exposure. The elimination of 1-MN with urine after single and repeated exposure to 1-MN occurred mainly in the samples collected during the first day of collection. Conclusions 1-Methylnaphthalene was rapidly eliminated from the blood and tissues of animals exposed by inhalation to 1-MN. In repeated exposure, there was probably a significant increase of 1-MN metabolism in rats exposed to low and high 1-MN doses. Under conditions of repeated 1-MN exposure, no significant systemic 1-MN accumulation could be observed. Int J Occup Med Environ Health 2018;31(6):763–77

Health risk in road transport workers. Part I. Occupational exposure to chemicals, biomarkers of effect

Motor vehicle emissions constitute a mixture of different chemicals: volatile organic solvents, polycyclic aromatic hydrocarbons, heavy metals, isocyanates, etc. Drivers working in car cabins are exposed to chemicals deriving from incomplete combustion of fuels, exhaust emissions from working engines and fuel evaporation. Concentrations of these substances are rather low and do not exceed the applicable hygiene standards, but some of them pose, or are suspected to pose, carcinogenic risk. The interaction of chemical substances with human cells and tissues can lead to a number of modifications of metabolic pathways at a cellular level. The first biological mechanism of metabolic modulation is an inflammatory state and oxidative stress generation. The aim of this review is to analyze biomarkers of effect and to assess the hazard of occupational exposure of drivers. Int J Occup Med Environ Health. 2019;32(3):267–8

Health risk in transport workers. Part II. Dietary compounds as modulators of occupational exposure to chemicals

Professional drivers are exposed to a number of factors that have a negative influence on their health status. These include vibrations, noise, the lack of fresh air in the car cabin, shift work (frequently at night), monotony resulting from permanent repetition of certain actions, static loads due to immobilization in a sitting position, stress resulting from the need to ensure safety in heavy traffic, as well as air pollution (dust, volatile organic substances, nitrogen and sulfur oxides, polycyclic aromatic hydrocarbons, heavy metals, dioxins, furans and others). Factors associated with the specificity of the profession of a driver, including exposure to chemical substances, result in an increased risk of the development of many diseases, i.e., obesity, diabetes, heart disease, hypertension, extensive genitourinary pathology experienced by taxi drivers, lung cancer and other forms of cancer. In the case of drivers, especially those covering long distances, there are also actual difficulties related to ensuring a proper diet. Although attempts at interventional research that would change the principles of nutrition, as well as ensure physical activity and weight reduction, have been made, their results have not been satisfactory. The paper focuses on the discussion on the role of a diet and dietary phytochemicals in the prevention of adverse health effects of such chemicals as a mix of chemicals in the polluted air, benzo(a)pyrene, benzene and metals (lead, cadmium, chromium, nickel), which are the main sources of exposure in the case of transport workers. Int J Occup Med Environ Health. 2019;32(4):441–6