Adaptive Effects of Intermittent Hypoxia Training on Oxygen-Dependent Processes as a Potential Therapeutic Strategy Tool.

BACKGROUND/AIMS: Important benefits of intermittent hypoxic training (IHT) have emerged as an effective tool for enhancing adaptive potential in different pathological states, among which acute hypoxia dominates. Therefore, the aim of our study was to evaluate the mechanisms related to the effects of the nitric oxide system (nitrites, nitrates, carbamide, and total polyamine content) on ADP-stimulated oxygen consumption and oxidative phosphorylation in heart and liver mitochondria and biomarkers of oxidative stress in the blood, heart, and liver of rats exposed to the IHT method and acute hypoxia and treated with the amino acid L-arginine (600 mg/kg, 30 min) or the NO synthase inhibitor L-NNA (35 mg/kg, 30 min) prior to each IHT session. METHODS: We analysed the modulation of the system of oxygen-dependent processes (mitochondrial respiration with the oxygraphic method, microsomal oxidation, and lipoperoxidation processes using biochemical methods) in tissues during IHT in the formation of short-term and long-term effects (30, 60, and 180 days after the last IHT session) with simultaneous administration of L-arginine. In particular, we investigated how mitochondrial functions are modulated during intermittent hypoxia with the use of oxidation substrates (succinate or α-ketoglutarate) in bioenergetic mechanisms of cellular stability and adaptation. RESULTS: The IHT method is associated with a significant increase in the production of endogenous nitric oxide measured by the levels of its stable metabolite, nitrite anion, in both plasma (almost 7-fold) and erythrocytes (more than 7-fold) of rats. The intensification of nitric oxide-dependent pathways of metabolic transformations in the energy supply processes in the heart and liver, accompanied by oscillatory mechanisms of adaptation in the interval mode, causes a probable decrease in the production of urea and polyamines in plasma and liver, but not in erythrocytes. The administration of L-arginine prior to the IHT sessions increased the level of the nitrite-reducing component of the nitric oxide cycle, which persisted for up to 180 days of the experiment. CONCLUSION: Thus, the efficacy of IHT and its nitrite-dependent component shown in this study is associated with the formation of long-term adaptive responses by preventing the intensification of lipoperoxidation processes in tissues due to pronounced changes in the main enzymes of antioxidant defence and stabilisation of erythrocyte membranes, which has a pronounced protective effect on the system of regulation of oxygen-dependent processes as a whole.

Role of antioxidants in the neurobiology of drug addiction: An update.

Relationships between protective enzymatic and non-enzymatic pro-antioxidant mechanisms and addictive substances use disorders (SUDs) are analyzed here, based on the results of previous research, as well as on the basis of our current own studies. This review introduces new aspects of comparative analysis of associations of pro-antixidant and neurobiological effects in patients taking psychoactive substances and complements very limited knowledge about relationships with SUDs from different regions, mainly Europe. In view of the few studies on relations between antioxidants and neurobiological processes acting in patients taking psychoactive substances, this review is important from the point of view of showing the state of knowledge, directions of diagnosis and treatment, and further research needed explanation. We found significant correlations between chemical elements, pro-antioxidative mechanisms, and lipoperoxidation in the development of disorders associated with use of addictive substances, therefore elements that show most relations (Pr, Na, Mn, Y, Sc, La, Cr, Al, Ca, Sb, Cd, Pb, As, Hg, Ni) may be significant factors shaping SUDs. The action of pro-antioxidant defense and lipid peroxidation depends on the pro-antioxidative activity of ions. We explain the strongest correlations between Mg and Sb, and lipoperoxidation in addicts, which proves their stimulating effect on lipoperoxidation and on the induction of oxidative stress. We discussed which mechanisms and neurobiological processes change susceptibility to SUDs. The innovation of this review is to show that addicted people have lower activity of dismutases and peroxidases than healthy ones, which indicates disorders of antioxidant system and depletion of enzymes after long-term tolerance of stressors. We explain higher level of catalases, reductases, ceruloplasmin, bilirubin, retinol, α-tocopherol and uric acid of addicts. In view of poorly understood factors affecting addiction, analysis of interactions allows for more effective understanding of pathogenetic mechanisms leading to formation of addiction and development the initiation of directed, more effective treatment (pharmacological, hormonal) and may be helpful in the diagnosis of psychoactive changes.

Palm oil as part of a high-fat diet: advances and challenges, or possible risks of pathology?

Nutritional status disorders have the most significant impact on the development of cardiovascular and oncologic diseases; therefore, the interest in the study of palm oil as among the leading components of nutrition has been increasing. The data examined in this review were sourced from the Scopus, SCIE (Web of Science), PubMed and PubMed Central, MEDLINE, CAPlus/SciFinder, and Embase databases; experts in the field; bibliographies; and abstracts from review analyses from the past 15 years. This review summarizes recent research data focusing on the quantitative and qualitative composition of nutrition of modern humans; concepts of the relationship between high-fat diets and disorders of insulin functioning and transport and metabolism of fatty acids; analyses of data regarding the palmitic acid (16:0) to oleic acid (18:1) ratio; and the effect of diet based on palm oil consumption on cardiovascular risk factors and lipid and lipoprotein levels. Several studies suggest a potential vector contributing to the transmission of maternal, high-fat-diet-induced, addictive-like behaviors and obesogenic phenotypes across generations. The relationship between cholesterol accumulation in lysosomes that may lead to lysosome dysfunction and inhibition of the autophagy process is analyzed, as is the progression of inflammatory diseases, atherosclerosis, nonalcoholic liver inflammation, and obesity with associated complications. Data are discussed from analyses of differences between rodent models and human population studies in the investigated different effects of palm oil consumption as a high-fat diet component. A conclusion is reached that the results cannot be generalized in human population studies because no similar effects were observed. Although there are numerous published reports, more studies are necessary to elucidate the complex regulatory mechanisms in digestive and nutrition processes, because there are great differences in lipoprotein profiles between rodents and humans, which makes it difficult to reproduce the pathology of many diseases caused by different types of the high-fat diet.

The Role of Glutathione in Age-Related Macular Degeneration (AMD).

Age-related macular degeneration (AMD) is a chronic disease that usually develops in older people. Pathogenetic changes in this disease include anatomical and functional complexes. Harmful factors damage the retina and macula. These changes may lead to partial or total loss of vision. The disease can occur in two clinical forms: dry (the progression is slow and gentle) and exudative (wet-progression is acute and severe), which usually starts in the dry form; however, the coexistence of both forms is possible. The etiology of AMD is not fully understood, and the precise mechanisms of the development of this illness are still unknown. Extensive genetic studies have shown that AMD is a multi-factorial disease and that genetic determinants, along with external and internal environmental and metabolic-functional factors, are important risk factors. This article reviews the role of glutathione (GSH) enzymes engaged in maintaining the reduced form and polymorphism in glutathione S-transferase theta-1 (GSTT1) and glutathione S-transferase mu-1 (GSTM1) in the development of AMD. We only chose papers that confirmed the influence of the parameters on the development of AMD. Because GSH is the most important antioxidant in the eye, it is important to know the influence of the enzymes and genetic background to ensure an optimal level of glutathione concentration. Numerous studies have been conducted on how the glutathione system works till today. This paper presents the current state of knowledge about the changes in GSH, GST, GR, and GPx in AMD. GST studies clearly show increased activity in ill people, but for GPx, the results relating to activity are not so clear. Depending on the research, the results also suggest higher and lower GPx activity in patients with AMD. The analysis of polymorphisms in GST genes confirmed that mutations lead to weaker antioxidant barriers and may contribute to the development of AMD; unfortunately, a meta-analysis and some research did not confirm that connection. Unspecific results of many of the parameters that make up the glutathione system show many unknowns. It is so important to conduct further research to understand the exact mechanism of defense functions of glutathione against oxidative stress in the human eye.

Analysis of the season-dependent component in the evaluation of morphological and biochemical blood parameters in Shetland ponies of both sexes during exercise.

Introduction: Determination of morphological and biochemical blood indices facilitates assessment of the health and welfare of horses, their nutrient demand, the effects of training already undertaken, and the horses' suitability for exercise. Identification of the season-dependent components and the effects of sex and exercise on changes in frequently referenced haematological and biochemical parameters was the main goal of the current study. Material and Methods: The blood morphology of 21 healthy adult Shetland ponies (11 mares and 10 stallions) aged 6.5 ± 1.4 years from the central Pomeranian region in Poland was analysed. Blood samples were taken once per season for one year. Results: No statistically significant season-dependent differences were found in the blood morphology parameters in either mares or stallions before or after exercise. Beta-coefficient results revealed the strength and type of the relationship of red blood cell distribution width (RDW) and granulocyte count (GRA) with the season, of red blood cell count (RBC), haematocrit, mean corpuscular volume and mean platelet volume with the sex, and of RDW, white blood cell count, GRA and RBC with the exercise factor. Biomarkers demonstrating the relationship between aerobic and anaerobic levels of energy metabolism in the blood did not show any sex dependency in regression analysis. Conclusion: The sex-independence of energy metabolism biomarkers may indicate the universality of these parameters. Both seasonality itself and its combination with the exercise factor took part in the formation of effective adaptive reactions for maintenance of morphological blood indices in the ponies during exercise.

Tricarboxylic Acid Cycle Intermediates and Individual Ageing.

Anti-ageing biology and medicine programmes are a focus of genetics, molecular biology, immunology, endocrinology, nutrition, and therapy. This paper discusses metabolic therapies aimed at prolonging longevity and/or health. Individual components of these effects are postulated to be related to the energy supply by tricarboxylic acid (TCA) cycle intermediates and free radical production processes. This article presents several theories of ageing and clinical descriptions of the top markers of ageing, which define ageing in different categories; additionally, their interactions with age-related changes and diseases related to α-ketoglutarate (AKG) and succinate SC formation and metabolism in pathological states are explained. This review describes convincingly the differences in the mitochondrial characteristics of energy metabolism in animals, with different levels (high and low) of physiological reactivity of functional systems related to the state of different regulatory systems providing oxygen-dependent processes. Much attention is given to the crucial role of AKG and SC in the energy metabolism in cells related to amino acid synthesis, epigenetic regulation, cell stemness, and differentiation, as well as metabolism associated with the development of pathological conditions and, in particular, cancer cells. Another goal was to address the issue of ageing in terms of individual characteristics related to physiological reactivity. This review also demonstrated the role of the Krebs cycle as a key component of cellular energy and ageing, which is closely associated with the development of various age-related pathologies, such as cancer, type 2 diabetes, and cardiovascular or neurodegenerative diseases where the mTOR pathway plays a key role. This article provides postulates of postischaemic phenomena in an ageing organism and demonstrates the dependence of accelerated ageing and age-related pathology on the levels of AKG and SC in studies on different species (roundworm Caenorhabditis elegans, Drosophila, mice, and humans used as models). The findings suggest that this approach may also be useful to show that Krebs cycle metabolites may be involved in age-related abnormalities of the mitochondrial metabolism and may thus induce epigenetic reprogramming that contributes to the senile phenotype and degenerative diseases. The metabolism of these compounds is particularly important when considering ageing mechanisms connected with different levels of initial physiological reactivity and able to initiate individual programmed ageing, depending on the intensity of oxygen consumption, metabolic peculiarities, and behavioural reactions.

Can blood morphology, oxidative stress, and cholinesterase activity determine health status of pigeon Columba livia f. urbana?

Environmental studies in Northern Poland are example of the functioning of ecophysiological relationships under anthropogenic impact. The aim of our studies was to investigate sex-dependent effects on the alterations in the concentration of chemical elements in soil samples collected from habitats of feral pigeon Columba livia f. urbana from Northern Poland, as well as feathers, biomarkers of oxidative stress, antioxidant defense, and total cholinesterase activity in tissues (liver, kidney, brain). Concentration of Si, Zn, and Pb in feathers of pigeons was significant. The levels of Si and Zn were higher in feathers of females from non-polluted, while higher Pb levels were found only in females from polluted areas (p = 0.000). This was confirmed by MANOVA of biomarkers of antioxidant defense, elements concentration, and revealing the order of effects: tissue type > environment > sex. Erythrocytes of males living in polluted areas were more fragile to hemolytic agents resulting in a higher percentage of hemolyzed erythrocytes. The effects of polluted environment on the level of carbonyl derivatives of oxidatively modified proteins compared to the effects of sex were more pronounced in the case of kidney (p = 0.000) and hepatic tissues (p = 0.000). Polluted areas were associated with significant increase in SOD activity in the brain and hepatic tissues of pigeons (p = 0.000). Health status of feral pigeons is significantly different in conditions of environmental destabilization.

Do the Effects of Krebs Cycle Intermediates on Oxygen-Dependent Processes in Hypoxia Mediated by the Nitric Oxide System Have Reciprocal or Competitive Relationships?

BACKGROUND/AIMS: Currently, it is proven that the cellular metabolism of nitric oxide is necessary to maintain optimal health and adaptation of the organism to the impact of various environmental factors. The aim of this work was to reveal the biological role of nitric oxide, its metabolic changes, and its mechanism of action in tissues under hypoxia, as well as the possibility of tissue metabolism correction through NO-dependent systems under the influence of Krebs cycle intermediates. METHODS: A systematic assessment of the effect of succinate (SC, 50 mg/kg b.w.) and α-ketoglutarate (KGL, 50 mg/kg b.w.) in the regulation of oxygendependent processes in rats (mitochondrial oxidative phosphorylation, microsomal oxidation, intensity of lipid peroxidation processes, and the state of the antioxidant defense system) depending on functional changes in nitric oxide production during hypoxia was evaluated. The state of the nitric oxide system was estimated spectrophotometrically by determination of the concentration of its stable nitrite anion metabolite (NO2 -). The levels of catecholamines were estimated from the content of epinephrine and norepinephrine using the differentially fluorescent method. The activity of cytochrome P450-dependent aminopyrine-N-demethylase was determined with the Nash reagent. RESULTS: Tissue hypoxia and metabolic disorders caused by this condition through changes in the content of catecholamines (epinephrine, norepinephrine, dopamine, DOPA) as well as the cholinesterase-related system (acetylcholine content and acetylcholinesterase activity) were the studied experimental parameters under acute hypoxia (AH, 7% O2 in N2, 30 min). The activation of lipid peroxidation and oxidatively modified proteins and an increase in the epinephrine content in AH are associated with an increased role of SC and a decrease in KGL as substrates of oxidation in mitochondria. A more pronounced effect of exogenous KGL, compared to SC, on the content of nitrite anion as a stable metabolite of nitric oxide in the liver under acute hypoxia against the background of a decrease in the intensity of lipid peroxidation processes was revealed. The activation of SC-dependent mitochondrial oxidative processes caused by AH was found to decrease in animals after an intermittent hypoxia training (IHT) course. IHT (7% O2 in N2, 15-min, 5 times daily, 14 days) prevented the activation of oxidative stress in tissues and blood after the AH impact and increased the efficiency of energy-related reactions in the functioning of hepatic mitochondria through increased oxidation of KGL. CONCLUSION: The studied effects of adaptation are mediated by an increase in the role of NO-dependent mechanisms, as assessed by changes in the pool of nitrates, nitrites, carbamides, and total polyamines.

Supplementation with l-arginine and nitrates vs age and individual physiological reactivity.

Ageing is a natural ontogenetic phenomenon that entails a decrease in the adaptive capacity of the organism, as a result of which the body becomes less adaptable to stressful conditions. Nitrate and nitrite enter the body from exogenous sources and from nitrification of ammonia nitrogen by intestinal microorganisms. This review considers the mechanisms of action of l-arginine, a known inducer of nitric oxide (NO) biosynthesis, and nitrates as supplements in the processes of ageing and aggravated stress states, in which mechanisms of individual physiological reactivity play an important role. This approach can be used as an element of individual therapy or prevention of premature ageing processes depending on the different levels of initial reactivity of the functional systems. A search was performed of the PubMed, Scopus, and Google Scholar databases (n = 181 articles) and the author's own research (n = 4) up to May 5, 2023. The review presents analyses of data on targeted treatment of NO generation by supplementation with l-arginine or nitrates, which is a promising means for prevention of hypoxic conditions frequently accompanying pathological processes in an ageing organism. The review clarifies the role of the individual state of physiological reactivity, using the example of individuals with a high predominance of cholinergic regulatory mechanisms who already have a significant reserve of adaptive capacity. In studies of the predominance of adrenergic influences, a poorly trained organism as well as an elderly organism correspond to low resistance, which is an additional factor of damage at increased energy expenditure. Conclusion: It is suggested that the role of NO synthesis from supplementation of dietary nitrates and nitrites increases with age rather than from oxygen-dependent biosynthetic reactions from l-arginine supplementation.

The Effectiveness of L-arginine in Clinical Conditions Associated with Hypoxia.

The review summarises the data of the last 50 years on the effectiveness of the amino acid L-arginine in therapeutic practice in conditions accompanied by different-origin hypoxia. The aim of this review was to analyse the literature and our research data on the role of nitric oxide in the modulation of individual physiological reactivity to hypoxia. The review considers the possibility of eliminating methodological conflicts in the case of L-arginine, which can be solved by taking into account individual physiological reactivity (or the hypoxia resistance factor). Considerable attention is paid to genetic and epigenetic mechanisms of adaptation to hypoxia and conditions of adaptation in different models. The article presents data on the clinical effectiveness of L-arginine in cardiovascular system diseases (hypertension, atherosclerosis, coronary heart disease, etc.) and stress disorders associated with these diseases. The review presents a generalised analysis of techniques, data on L-arginine use by athletes, and the ambiguous role of NO in the physiology and pathology of hypoxic states shown via nitric oxide synthesis. Data on the protective effects of adaptation in the formation of individual high reactivity in sportsmen are demonstrated. The review demonstrates a favourable effect of supplementation with L-arginine and its application depending on mitochondrial oxidative phosphorylation processes and biochemical indices in groups of individuals with low and high capacity of adaptation to hypoxia. In individuals with high initial anti-hypoxic reserves, these favourable effects are achieved by the blockade of NO-dependent biosynthesis pathways. Therefore, the methodological tasks of physiological experiments and the therapeutic consequences of treatment should include a component depending on the basic level of physiological reactivity.

Invitro impact of a combination of red and infrared LEDs, infrared laser and magnetic field on biomarkers of oxidative stress and hemolysis of erythrocytes sampled from healthy individuals and diabetes patients.

AIMS: Low-intensity infrared laser irradiation with output emissions of the laser and LED for in vitro irradiation of plasma and erythrocyte samples collected from healthy individuals and diabetes mellitus (DM) patients was used in the current study. METHODS: The generated emission was in the range 0.85-0.89 nm with pulse duration near 130 ns and repetition rates of pulses 50, 150, 600, and 1500 Hz, average power 0, 50, or 100 mW, in the range of 1-9 min for different 30 variants of irradiation. The levels of 2-thiobarbituric-acid reactive substances (TBARS), aldehydic and ketonic derivatives of oxidatively modified proteins (OMP), total antioxidant capacity (TAC), acid-induced resistance of erythrocytes, and activities of the main antioxidant enzymes were assessed in erythrocyte and plasma samples after irradiation. RESULTS: The low-intensity infrared laser irradiation and low-intensity light emitted by a red LED decreased the lipid peroxidation levels in the erythrocytes of both healthy individuals and DM patients. A statistically significant decrease in TBARS and OMP levels and an increase in the TAC level were observed at the irradiation energy of 34.39 and 68.79 J/cm2 for samples collected from both healthy individuals and DM patients. The effects of the irradiation were accompanied by a statistically significant decrease in catalase activity of both healthy individuals and DM patients. CONCLUSIONS: In many variants of the laser irradiation and low-intensity light emitted by a red LED used in our study, a decrease in the percent of hemolyzed erythrocytes was observed, suggesting that laser therapy protocols should take into account fluencies, frequencies, and wavelengths of the laser before the beginning of treatment, especially in DM patients.

Photoperiod-dependent changes in oxidative stress markers in the blood of Shetland pony mares and stallions involved in recreational horseback riding.

The objective of the current study was to determine the photoperiod-induced variations and the impact of exercise on oxidative stress biomarkers [2-thiobarbituric acid reactive substances (TBARS), aldehydic (AD) and ketonic (KD) derivatives of oxidatively modified proteins (OMP), total antioxidant capacity (TAC), and activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx)] and biomarkers of metabolic alterations [glucose, urea, and uric acid and the activity of lactate dehydrogenase (LDH)] in the blood of Shetland pony mares and stallions involved in recreational horseback riding. Twenty-one healthy adult Shetland ponies (11 mares and 10 stallions) aged 6.5 ± 1.4 years old from the central Pomeranian region in Poland were used in this study. Blood samples were taken once per season for one year: spring (3 April), summer (5 July), autumn (1 October) and winter (25 January). A MANOVA analysis revealed that the photoperiod factor had a leading role in alterations of these biomarkers, while the exercise and sex of the ponies exerted a lower impact. The lipid peroxidation biomarkers, for example, the plasma TBARS level, indicated the maximum adjusted coefficient of determination R2ad = 0.77. Before exercise (at rest), the plasma of the stallions and mares exhibited minimum values of TBARS levels in the spring and summer photoperiods and maximum levels in autumn and winter. A statistically significant reduction in the levels of both aldehydic and ketonic derivatives of OMP in the blood of ponies was observed during the autumn and winter periods; additionally, the level of ketonic derivatives of OMP declined after exercise in spring. TAC was statistically significant in the spring and winter photoperiods both before and after exercise. SOD activity did not have a pronounced photoperiod-induced pattern but was dependent on the sex and exercise. CAT activity varied and was statistically significant only in the plasma of the mares after exercise in the spring, summer, and winter photoperiods. The minimum GPx activity in the blood of the mares before exercise (at rest) was observed in autumn, while the maximum was noted in winter and summer. Photoperiod- and exercise-induced alterations in markers of oxidative stress and antioxidant defences may contribute to the adaptation of animals to exercise, depending on sex. The seasonal variations in the antioxidant defences demonstrated in our study, as well as substrates of energy metabolism in the blood of mares and stallions, depending on exercise capacity, could be an important aspect in the ability of endogenous adaptive mechanisms of animals to react in advance to environmental changes associated with seasons.

Do the diverse environments of Baltic coastal zone affect hematological and biochemical alterations in the blood of mute swans (Cygnus olor)?

Based on studies of the wintering population of mute swans in large urban agglomerations, it is possible to identify and infer the impact of environmental pollution in coastal regions near Baltic Sea on the physiological and biochemical changes in the blood of waterfowls. Hematological and biochemical changes in the blood in relation to chemical elements in their feathers are a useful tool for general ecophysiological conclusions. Hematological changes and blood chemistry in Mute Swan Cygnus olor is particularly environmentally dependent, therefore we examined hematological picture (red blood cells RBC, white blood cells WBC, heterophiles, eosinophils, basophils, monocytes, lymphocytes, hemoglobin, heterophile to lymphocyte ratio H/L, biochemical indicators (glucose, uric acid, total cholesterol, triglycerides, calcium, inorganic phosphorus, magnesium, total protein), stability of erythrocyte membranes, concentration of Ca, P, Mg in the blood, concentration of Al, Zn, Rh, Cu, Ru, Fe, Pb in feathers, in wintering population of 172 mute swans of different age (juvenile, adult) and gender, in three coastal types of areas of Southern Polish zone of Baltic Sea (Slupsk, Gdynia, Sopot). Percentage of changes in the morphological indices in the blood of mute swans with three independent characteristics (environment, sex, age) revealed that hemoglobin content exhibited the highest value (R2 = 53.8%) in the analysis of morphological indices; the effect of RBC, WBC, and basophils was much lower (WBC > RBC > basophils). Male and female erythrocytes from the coastal of Gdynia were more fragile than those of birds from coasts of Sopot and Slupsk. We found that osmotic fragility is altered in juvenile swans from Slupsk area and males from Gdynia area. The consequence was a higher level of hemolyzed erythrocytes in their blood. The effect of type of environment, age-, and sex-related impact on hematological indices and biomarkers of biochemical alterations in the blood of swans and comparison of these data with bioaccumulation of chemical elements in feathers of swans inhabiting 3 types of environment of Baltic coastal zone show significant differences in the hematological and biochemical indices. Albumins and globulins maintain the blood cations balance, however, changes in their concentrations in the blood suggest an impact on physiological mechanisms and body condition of swans.

Enzymatic Antioxidant Defense and Polymorphic Changes in Male Infertility.

The intensification of oxidative stress and destabilization of the antioxidative defenses of an organism is a consequence of many environmental factors. We considered aspects conditioning male reproductive potential and the functionality of enzymatic antioxidative mechanisms, i.e., superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR), and their correlations with Li, Be, B, Na, Mg, Al, P, K, Ca, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se, Sr, Mo, Ag, Cd, Sn, Sb, Ba, Hg, Tl, Pb, and malondialdehyde (MDA), as well as genetic polymorphism IL-4v.C589T (rs2243250) in men with infertility (n = 76). A healthy normozoospermic control (n = 87) was also used. We assessed the impact of negative changes driven by oxidative stress on enzymatic antioxidative mechanisms as well as the role of MDA in the overall process. On this basis, we infer connections between disturbances in enzymatic antioxidative defense and reproductive potential. Based on a molecular analysis of the polymorphism of gene IL-4v.C589T (rs2243250) (chromosome 5) (PCR-RFLP), we considered the relationships among particular genotypes with the possibility of occurrence of male infertility. Concentrations of chemical elements were measured in the blood. The activity of antioxidants and MDA levels were measured in serum. In the infertile group, higher GPx activity was noted (6.56 nmoL·min-1·mL-1, control: 4.31 nmoL·min-1·mL-1; p = 0.004), while GR achieved a greater level in the control (17.74 nmoL·min-1·mL-1, infertile: 15.97 nmoL·min-1·mL-1, p = 0.043), which implies diversified efficiency of the first and second lines of defense. The polymorphism of IL-4v.C589T (rs2243250) was not directly connected with infertility because there were not any differences in the frequency of genotypes between the infertile and control group (p = 0.578). An analysis of genotypes CC and TT (polymorphism IL-4v.C589T (rs2243250)) indicated numerous correlations between antioxidants, chemical elements and MDA. Therefore, chemical economy, antioxidative defense and genetic conditions are connected and jointly shape male reproductive potential. Chemical elements influence antioxidative defense and male fertility; the most important modulators appeared to be Na, Ba, Al and B. The polymorphism of gene IL-4v.C589T (rs2243250) has a limited influence on antioxidative defense and the metabolism of chemical elements.

Effects of melatonin and metformin in preventing lysosome-induced autophagy and oxidative stress in rat models of carcinogenesis and the impact of high-fat diet.

Imbalanced glucose tolerance and insulin resistance remain important as high cancer risk factors. Metformin administration to diabetic patients may be associated with a reduced risk of malignancy. The combined effects of the hormone melatonin and metformin in oncology practice have shown positive results. The relevance of our study is to find out the role of specific biomarkers of lysosome destruction and oxidative stress data in carcinogenesis models. The present study was designed to investigate the comparative synergic effect of peroral antidiabetic metformin (MF) and pineal hormone melatonin (MEL) administered alone and in combination in two different rat's models of mammary tumour proliferation in vivo (N-methyl-N-nitrosourea, NMU or 7,12-dimethylbenz[a]anthracene, DMBA). We have studied the processes of lysosomal destruction (alanyl aminopeptidase AAP, leucyl aminopeptidase LAP, acid phosphatase AcP, ß-N-acetylglucosaminidase NAG, ß-galactosidase ß-GD and ß-glucuronidase ß-GR) caused by evaluated oxidative stress in three types of tissues (liver, heart, and spleen) in female Sprague-Dawley rats fed a high-fat diet (10% of total fat: 2.5% from lard and 7.5% from palm olein). Our results revealed an increase in the activity of the studied lysosomal enzymes and their expression in a tissue-specific manner depending on the type of chemical agent (NMU or DMBA). MANOVA tests in our study confirmed the influence of the three main factors, type of tissue, chemical impact, and chemopreventive agents, and the combinations of these factors on the lysosomal activity induced during the process of cancerogenesis. The development and induction of the carcinogenesis process in the different rat models with the high-fat diet impact were also accompanied by initiation of free-radical oxidation processes, which we studied at the initial (estimated by the level of diene conjugates) and final (TBARS products) stages of this process. The combined effects of MEL and MF for the two models of carcinogenesis at high-fat diet impact for AAP, LAP, and AcP showed a significant synergistic effect when they impact together when compared with the effects of one substance alone (either MEL or MF) in the breast cancer model experiments. Synergistic effects of limiting destructive processes of lysosomal functioning ß-GD enzyme activity we obtained in experiments with MEL and MF chemoprevention for both models of carcinogenesis for three tissues. The statistical SS test allowed us to draw the following conclusions on the role of each lysosomal parameter analyzed as an integral model: NAG > AcP > ß-GD > ß-GR > AAP > LAP.

Biomarkers of oxidative stress, metabolic processes, and lysosomal activity in the muscle tissue of the great tit (Parus major) living in sodium industry and agricultural areas in Inowroclaw region (central part of northern Poland).

An region of ecological hazard (EHR) is an area where, as a result of intensive human economic activity, degradation of components of the natural environment has taken place, leading to the deterioration of the ecological balance. EHR management is a globalised ever-increasing challenge. To eliminate the hazardous effect of these pollutants, research has been accelerated worldwide. The current study analyzed the specific biomarkers of the lipid and protein oxidation, total antioxidative status, activities of antioxidant enzymes (superoxide dismutase, catalase, glutathione reductase and peroxidase), lysosomal enzymes (alanyl aminopeptidase, leucyl aminopeptidase, acid phosphatase), and biomarkers of aerobic and anaerobic metabolic pathways (activities of alanine and aspartate aminotransferases, succinate dehydrogenase, lactate dehydrogenase, lactate and pyruvate levels) in skeletal muscle tissue of wild great tit nestlings in environments with different levels of anthropogenic pressure such as sodium industry and agriculture in the central part of northern Poland (Inowroclaw EHR). Control samples were collected from Tuchola Forest and Borkowo village, where no direct sources of contamination were found. The relevance of the study was to assess the changes in lysosomal functioning caused by pollution-induced oxidative stress that may indicate multidirectional adaptative mechanisms of metabolic processes occurring in the wild birds to compensate for the negative effects of contamination. It was shown that the initiation of oxidative stress caused by anthropogenic pollution shifted the balance of the normal functioning of lysosomal enzymes towards their increased activity. A general tendency towards an increase in the intensity of lipid peroxidation processes with an increasing level of oxidatively modified proteins (aldehydic and ketonic derivatives) and a simultaneous reduction in the TAS was observed in the muscle tissue of great tits living in the anthropogenically modified areas. The intensity of lipid peroxidation and protein damage caused changes and reorganization of the energy-related metabolic pathways in the muscle tissue of wild great tits living in the sodium industry and agricultural areas of the EHR.

Relationship Between Thyroid Hormonal Status in Patients with a Hypothyroid Form of Hashimoto's Thyroiditis and Iodine Concentrations in Drinking Water.

The current study aimed to identify correlative and regressive dependencies between the water iodine concentration and the levels of TSH (thyroid-stimulating hormone), thyroglobulin antibodies (TgAbs), and thyroid peroxidase (TPOAb) in the serum of 168 in patients (34 men and 134 women) with a hypothyroid form of Hashimoto's thyroiditis who use water from the supply network and individual wells. Based on the water iodine concentration, low and moderate degrees of iodine endemia in the location of the patients were determined. In the groups of men and women using water from different water supply sources, there were direct correlations between the water iodine concentrations and the TgAbs and TPOAb titers as well as an inverse dependence between iodine and TSH levels. Multivariate regressive analysis indicated that TgAb and TSH in the group of women using water from a supply network and TPOAb titers in the group of women using well water were independent factors associated with water iodine concentrations. Statistically significant correlations and regressive dependencies between the water iodine concentrations and the biomarkers of the thyroid status of the patients indicate the risk of Hashimoto's thyroiditis progression, especially among women with additional iodine intake.

Habitat-, age-, and sex-related alterations in oxidative stress biomarkers in the blood of mute swans (Cygnus olor) inhabiting pomeranian coastal areas (Northern Poland).

The mute swan (Cygnus olor) can be considered a representative species of birds associated with the aquatic environment and responding very clearly to changes in the environment. Assuming that the condition of the mute swan population well reflects the state of the environment, this species was used in our research as a bioindicative species. Thus, the aim of our study was to elucidate the association between metal contents in soil samples collected from a habitat of mute swans and element contents in their feathers as well as the levels of biomarkers of lipid peroxidation, oxidatively modified proteins, and total antioxidant capacity in the blood of mute swans living in three agglomerations in coastal areas in the southern part of the Baltic Sea (Pomeranian region, northern Poland). We compared the effects of inhabitation, age, and sex on the ecophysiological accumulation of metals in three wintering populations of the mute swan from coastal areas of northern Poland, i.e., Slupsk, Gdynia, and Sopot. In Slupsk, the anthropogenic pressure was related predominantly to the level of Al and, to a lesser extent, to the content of Rh and Ru. We found maximum levels of lipid peroxidation biomarkers in the blood of the mute swans from Gdynia (38.20 ± 6.35 nmol MDA·mL-1). At the same time, maximum levels of aldehydic and ketonic derivatives of oxidatively modified proteins were noted in the blood of swans from Sopot compared to the values obtained in mute swans from Slupsk and Gdynia. This trend suggesting high levels of oxidative stress biomarkers was also confirmed by a decrease in the total antioxidant capacity in these groups.

A Comparison of Oxidative Stress Biomarkers in the Serum of Healthy Polish Dairy Goats with Those Naturally Infected with Small Ruminant Lentivirus in the Course of Lactation.

The present study examines the effects of natural infection by small ruminant lentivirus (SRLV) in the two most common goat breeds in Poland, i.e., Polish white improved and polish fawn improved. It focuses on biomarkers of oxidative stress, oxidatively modified proteins and antioxidant defenses, ceruloplasmin level as an acute phase protein, and the activities of antioxidant enzymes in the goat serum. It was conducted on 24 goats divided into two equal groups: one SRLV-seropositive (SRLV-SP) and another SRLV-seronegative (SRLV-SN). Both groups were identical in terms of breed and parity. Despite infection, the SRLV-SP goats demonstrated no symptoms of caprine arthritis-encephalitis. In addition, the SRLV-SP goats did not reveal pronounced dysfunctions in oxidative stress biomarkers in the serum compared to the SRLV-SN animals. However, both groups demonstrated elevated levels of the aldehydic and ketonic derivatives of oxidatively modified proteins during the lactation period. In addition, both groups retained a high total antioxidant capacity in serum despite the decrease of enzyme antioxidant defenses throughout the 200-day lactation period.

Photoperiod-induced alterations in biomarkers of oxidative stress and biochemical pathways in rats of different ages: Focus on individual physiological reactivity.

Effects of photoperiodicity caused by both the age and individual physiological reactivity estimated by resistance to hypobaric hypoxia on the levels of lipid peroxidation, protein oxidation (aldehydic and ketonic derivatives), total antioxidant capacity, activities of antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase), and biochemical parameters of aerobic and anaerobic pathways in hepatic tissue depending on the blood melatonin level were studied. The study was carried out on 96 6- and 21-month-old male rats divided into hypoxia resistance groups (LR, low resistance, HR, high resistance). The analyses were conducted at four photoperiods: winter (January), spring (March), summer (July), and autumn (October). Our results indicate a significant effect of melatonin, i.e. over 80%, revealed by the complete statistical model of the studied biomarkers of oxidative stress and oxygen-dependent parameters of metabolism. The effects of melatonin vary with age and between photoperiods, which in turn was determined by individual physiological reactivity. In terms of the photoperiods, the melatonin content in the group of the adult animals with low resistance to hypoxia decreased from winter to summer. In a group of old animals in comparison with adults, the melatonin content in all the studied photoperiods was much lower as well, regardless of their hypoxia resistance. In the group of old animals with low resistance to hypoxia, the melatonin content decreased throughout the photoperiods as follows: winter, autumn, summer, and spring. As can be concluded, spring is a critical period for old animals, particularly those with low hypoxia resistance. The important role of melatonin in these processes was also confirmed by our correlation analysis between oxidative stress biomarkers, energy-related metabolites, and antioxidant enzymes in the hepatic tissue of rats of different ages, with different resistance to hypoxia, and in different photoperiods. The melatonin concentration in the blood of highly resistant rats was higher than in those with low resistance to hypoxia. Melatonin determines the individual constitutional level of resistance to hypoxia and is responsible for individual enzymatic antioxidative responses, depending on the four photoperiods. Our studies have shown that melatonin levels are related to the redox characteristics of antioxidant defenses against lipid peroxidation and oxidative modification of proteins in old rats with low resistance to hypoxia, compared to a group of highly resistant adults. Finally, the melatonin-related mechanisms of antioxidative protection depend on metabolic processes in hepatic tissue and exhibit photoperiodical variability in adult and old rats.