Genotoxic effects in the buccal cells of students exposed to season-associated increase of air pollution in Prishtina urban area: a preliminary study

The available monitoring data from Kosovo Environmental Protection Agency show concerning levels of the air pollution in Prishtina - the capital city of Kosovo and the most populated city in the country. Due to the air pollutants emitted mostly from the heavy traffic and the coal-fired power plants located in the vicinity, the residents of urban area in Prishtina are exposed to unhealthy air. It is reported that the situation worsens during the autumn and winter months due to more frequent smog episodes. Based on the concerns raised, the aim of the study was to assess the eventual genotoxic effects of air pollution among residents of Prishtina during the autumn and winter months. For this purpose, 29 healthy female non-smoker students (aged 20-26) were involved in this preliminary study. The first sampling of buccal cells took place beginning of November 2019 whereas the second sampling took place by the end of January 2020. Buccal cell samples were analyzed for the frequency of micronuclei and the obtained data demonstrate increased genotoxicity in a sample population as an effect of the exposure to increased air pollution levels in Prishtina urban area during the autumn and winter period. On the other hand, these preliminary data clearly indicate the need for continuing with bio-monitoring studies by extending the timeframe and increasing the number of seasons under investigation

Frequency Distribution and Association of some Morpho- and Physiological Traits in Patients with Lung Diseases in Kosova

The aim of this study was to investigate the distribution of specific phenotypes in patients with lung diseases as well as their eventual association withthe risk of developing lung diseases. For this purpose 2777 patients with lung diseases and 2778 healthy individuals from all over Kosova were examined for the appearance of the following selected phenotypes: ear lobe free (ELF)/ ear lobe attached, normal chin (NC)/cleft chin, tongue roller (TR)/non roller, hand clasping right thumb over (HC)/ hand clasping left thumb over, righthanded (RH)/lefthanded. In addition, the blood group from ABO system and the presence or absence of the Rhesus factor as phenotypical markers were observed. The results obtained show significant differences between control and lung disease patients for NC (P≤0.05) and TR (P≤0.005) as well as for blood groups AB (P≤0.05) and O (P≤0.005). These results point to eventually increased levels of genetic load as a result of the increased homozygosity in some gene loci causing an increased frequency of some recessive phenotypes in patients with lung diseases. Together with the specific associations observed, these preliminary findings could serve as a basis for further in depth investigations with respect to the types of lung diseases, occupational exposure and dietary habits, and thus is expected to contribute to an understanding of predispositions and susceptibility to lung diseases

From Pinocytosis to Methuosis—Fluid Consumption as a Risk Factor for Cell Death

The volumes of a cell [cell volume (CV)] and its organelles are adjusted by osmoregulatory processes. During pinocytosis, extracellular fluid volume equivalent to its CV is incorporated within an hour and membrane area equivalent to the cell’s surface within 30 min. Since neither fluid uptake nor membrane consumption leads to swelling or shrinkage, cells must be equipped with potent volume regulatory mechanisms. Normally, cells respond to outwardly or inwardly directed osmotic gradients by a volume decrease and increase, respectively, i.e., they shrink or swell but then try to recover their CV. However, when a cell death (CD) pathway is triggered, CV persistently decreases in isotonic conditions in apoptosis and it increases in necrosis. One type of CD associated with cell swelling is due to a dysfunctional pinocytosis. Methuosis, a non-apoptotic CD phenotype, occurs when cells accumulate too much fluid by macropinocytosis. In contrast to functional pinocytosis, in methuosis, macropinosomes neither recycle nor fuse with lysosomes but with each other to form giant vacuoles, which finally cause rupture of the plasma membrane (PM). Understanding methuosis longs for the understanding of the ionic mechanisms of cell volume regulation (CVR) and vesicular volume regulation (VVR). In nascent macropinosomes, ion channels and transporters are derived from the PM. Along trafficking from the PM to the perinuclear area, the equipment of channels and transporters of the vesicle membrane changes by retrieval, addition, and recycling from and back to the PM, causing profound changes in vesicular ion concentrations, acidification, and—most importantly—shrinkage of the macropinosome, which is indispensable for its proper targeting and cargo processing. In this review, we discuss ion and water transport mechanisms with respect to CVR and VVR and with special emphasis on pinocytosis and methuosis. We describe various aspects of the complex mutual interplay between extracellular and intracellular ions and ion gradients, the PM and vesicular membrane, phosphoinositides, monomeric G proteins and their targets, as well as the submembranous cytoskeleton. Our aim is to highlight important cellular mechanisms, components, and processes that may lead to methuotic CD upon their derangement

Antioxidants / Effects of -carotene and its cleavage products in primary pneumocyte type II cells

-Carotene has been shown to increase the risk of developing lung cancer in smokers and asbestos workers in two large scale trails, the Beta-Carotene and Retinol Efficacy Trial (CARET) and the Alpha-Tocopherol Beta-carotene Cancer Prevention Trial (ATBC). Based on this observation, it was proposed that genotoxic oxidative breakdown products may cause this effect. In support of this assumption, increased levels of sister chromatid exchanges, micronuclei, and chromosomal aberrations were found in primary hepatocyte cultures treated with a mixture of cleavage products (CPs) and the major product apo-8′carotenal. However, because these findings cannot directly be transferred to the lung due to the exceptional biotransformation capacity of the liver, potential genotoxic and cytotoxic effects of -carotene under oxidative stress and its CPs were investigated in primary pneumocyte type II cells. The results indicate that increased concentrations of -carotene in the presence of the redox cycling quinone dimethoxynaphthoquinone (DMNQ) exhibit a cytotoxic potential, as evidenced by an increase of apoptotic cells and loss of cell density at concentrations > 10 M. On the other hand, the analysis of micronucleated cells gave no clear picture due to the cytotoxicity related reduction of mitotic cells. Last, although CPs induced significant levels of DNA strand breaks even at concentrations 1 M and 5 M, respectively, -carotene in the presence of DMNQ did not cause DNA damage. Instead, -carotene appeared to act as an antioxidant. These findings are in contrast with what was demonstrated for primary hepatocytes and may reflect different sensitivities to and different metabolism of -carotene in the two cell types.(VLID)219514

Oxidative Stress and the Homeodynamics of Iron Metabolism

Iron and oxygen share a delicate partnership since both are indispensable for survival, but if the partnership becomes inadequate, this may rapidly terminate life. Virtually all cell components are directly or indirectly affected by cellular iron metabolism, which represents a complex, redox-based machinery that is controlled by, and essential to, metabolic requirements. Under conditions of increased oxidative stress—i.e., enhanced formation of reactive oxygen species (ROS)—however, this machinery may turn into a potential threat, the continued requirement for iron promoting adverse reactions such as the iron/H2O2-based formation of hydroxyl radicals, which exacerbate the initial pro-oxidant condition. This review will discuss the multifaceted homeodynamics of cellular iron management under normal conditions as well as in the context of oxidative stress

Peter Eckl: Research on the Pro-/Antioxidant Balance

Peter Maria ECKL started his scientific career in the late 1970s at the Paris-Lodron University of Salzburg working in the field of radiation research [...

Biomolecules / Oxidative stress and the homeodynamics of iron metabolism

Iron and oxygen share a delicate partnership since both are indispensable for survival, but if the partnership becomes inadequate, this may rapidly terminate life. Virtually all cell components are directly or indirectly affected by cellular iron metabolism, which represents a complex, redox-based machinery that is controlled by, and essential to, metabolic requirements. Under conditions of increased oxidative stressi.e., enhanced formation of reactive oxygen species (ROS)however, this machinery may turn into a potential threat, the continued requirement for iron promoting adverse reactions such as the iron/H2O2-based formation of hydroxyl radicals, which exacerbate the initial pro-oxidant condition. This review will discuss the multifaceted homeodynamics of cellular iron management under normal conditions as well as in the context of oxidative stress

4-Hydroxy-nonenal—A Bioactive Lipid Peroxidation Product

This review on recent research advances of the lipid peroxidation product 4-hydroxy-nonenal (HNE) has four major topics: I. the formation of HNE in various organs and tissues, II. the diverse biochemical reactions with Michael adduct formation as the most prominent one, III. the endogenous targets of HNE, primarily peptides and proteins (here the mechanisms of covalent adduct formation are described and the (patho-) physiological consequences discussed), and IV. the metabolism of HNE leading to a great number of degradation products, some of which are excreted in urine and may serve as non-invasive biomarkers of oxidative stress

Cytotoxicity of β-carotene cleavage products and its prevention by antioxidants

When we investigated the genotoxicity of β-carotene cleavage products (CPs) in primary rat hepatocytes stimulated to proliferate, we observed dose-dependent increases of chromosomal aberrations, sister chromatid exchanges and micronuclei. In contrast to other genotoxic substances, however, this increased genotoxicity was not accompanied by increased cytotoxicity. As a consequence we observed metaphases showing massive chromosomal damage, indicating inhibition of apoptosis by CPs enabling these cells to proceed in the cell cycle. Since proliferative stimulation by growth factors may support this effect, the in vitro toxicological effects of CPs were studied on proliferatively quiescent primary rat hepatocytes. A significant increase of both apoptosis and necrosis was found. Supplementation with antioxidants did not significantly lower the level of apoptosis, while the level of necrosis was significantly reduced by Trolox and N-acetylcysteine at all concentrations tested as well as ascorbic acid (50 µM) and a combination of Trolox (50 µM) and ascorbic acid (50 µM). These observations indicate that a) the cytotoxic potential in combination with the genotoxic potential of CPs may promote the initiation of cells due to compensatory cell division in exposed tissues and may aggravate inflammatory processes under chronic exposure, and b) the applied antioxidants may protect from cytotoxicity primarily via the detoxification of aldehydic β-carotene cleavage products

Pain and mobility improvement and MDA plasma levels in degenerative osteoarthritis, low back pain, and rheumatoid arthritis after infrared A-irradiation

Infrared (IR)-A irradiation can be useful in back and musculoskeletal pain therapy. In this study joint and vertebral column pain and mobility were measured during two weeks of IR-A irradiation treatment of patients suffering from degenerative osteoarthritis of hip and knee, low back pain, or rheumatoid arthritis. Additionally, before and after IR-A treatment MDA serum levels were measured to check if MDA variations accompany changes in pain intensity and mobility. Two-hundred and seven patients were divided into verum groups getting IR-irradiation, placebo groups getting visible, but not IR irradiation, and groups getting no irradiation. In osteoarthritis significant pain reduction according to Visual Analogue Scale and mobility improvements occurred in the verum group. Even though beneficial mean value changes occurred in the placebo group, the improvements in the placebo and No Irradiation groups were without statistical significance. In low back pain, pain and mobility improvements (by 35-40%) in the verum group were found, too. A delayed (2nd week) mobility improvement in rheumatoid arthritis was seen. However, pain relief was seen immediately. In patients suffering from low back pain or rheumatoid arthritis, the pain and mobility improvements were accompanied by significant changes of MDA serum levels. However, MDA appears not a sensitive biofactor for changes of the pain intensity in degenerative osteoarthritis. Nevertheless, unaffected or lowered MDA levels during intensive IR-A therapy argue against previous reports on free radical formation upon infrared. In conclusion, rapid beneficial effects of IR-A towards musculoskeletal pain and joint mobility loss were demonstrated