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The very-low calorie ketogenic diet (VLCKD) is recommended as an effective dietary approach for the management of obesity. This study investigated changes in circulating biomarkers of redox homeostasis induced by a multiphase VLCKD in obese individuals. A total of 40 obese subjects were prescribed a multiphasic VLCKD for eleven weeks. Anthropometric measurements, body composition parameters, calorimetric measures, and standard laboratory markers of glucose and lipid metabolism were evaluated at baseline (T0) and at the end of the dietary intervention (T1). Additionally, circulating markers of oxidative damage and antioxidant status were analyzed in serum and erythrocytes. Compared to T0, at T1 the multiphase VLCKD induced significant weight loss and reduction of waist circumference, with beneficial effects on body composition parameters and the glucose/lipid biochemical profile. Moreover, a decrease in serum markers of oxidative damage was reported at T1, while no changes in serum markers of antioxidant status and in erythrocyte redox markers were observed. In addition, a significant association was found between variations in anthropometric measurements, body composition, glucose metabolism parameters, and changes in circulating markers of oxidative damage. Regression models showed that variation in lipofuscin was significant predictor of changes in body mass index, fat mass, visceral adiposity, and insulin sensitivity. In conclusion, this study demonstrated that the multiphase VLCKD improves serum redox balance by reducing markers of oxidative damage in obese individuals, highlighting the interplay between adiposity, glucose metabolism, and redox homeostasis in the pathogenesis of obesity. Furthermore, these data provide a rationale for future investigations aimed at testing serum lipofuscin as a reliable redox marker in obesity.
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PURPOSE: This study focused on the selected markers of oxidative stress, impact of elevated lead levels on long-term hearing quality. We investigated whether the presence of certain essential minerals might provide protection to the auditory system against the effects of lead (and cadmium) compounds. METHODS: The research group included 280 male employees of the zinc and lead smelter, which was divided into: L-Pb-low blood lead concentration (PbB) subgroup, H-Pb-high PbB subgroup. Hearing tests were performed using the click evoked otoacoustic emission (CEOAE). RESULTS: Zinc protoporphyrin level was significantly higher in the H-Pb subgroup by 68%. Cd concentration was significantly higher in H-Pb by 33%. The Ca concentration was significantly lower in the H-Pb by - 2%. Selected oxidative stress markers concentration were significantly higher in the H-Pb group: malondialdehyde (MDA) by 4%, and lipofuscin (LPS) by 9%. In the CEOAE results showed statistically significant differences between the L-Pb and H-Pb subgroups. Larger negative changes in otoemission amplitude were observed in H-Pb subgroup. All otoemission results showed a statistically significant negative correlation with age, time of work, MDA concentration, and with PbB. Selected CEOAE parameters showed a significant negative correlation with cadmium blood concentration (CdB), and a positive correlation with Ca and Zn. CONCLUSION: Elevated blood lead content in occupational exposure is associated with an increase in MDA and LPS concentration, which negatively correlates with CEOAE parameters. This suggests an important role of oxidative stress in the long-term deterioration of hearing.
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The present study investigated associations between environmental exposure to cobalt (Co) and the levels of oxidative stress parameters and the antioxidant defense system in the seminal plasma of fertile males. The study population consisted of 117 healthy, non-smoking, fertile men from the southern region of Poland. The study was carried out in 2021-22. Based on the median cobalt levels in seminal plasma, subjects were divided into two groups: those with low (Co-L) and high (Co-H) cobalt concentrations. Semen parameters assessed according to WHO 2021 recommendations. After the analysis of spermiograms, observed reduction in progressive motility after 1 h was found in the Co-H group. Moreover, superoxide dismutase (SOD), glutathione S-transferase (GST) in the Co-H group had lower activity and GR higher activity. The OSI (Oxidative stress index) were higher in the group with high cobalt concentration in semen. The concentrations of redox balance parameters: TOS, TAC and OSI significantly were higher in the Co-high group as well as GR activity. Environmental exposure to cobalt decreases sperm motility in both normal and abnormal semen. The findings from this study affirm that cobalt can induce oxidative stress and alter oxidative stress markers in semen.
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Infertilidad Masculina , Análisis de Semen , Humanos , Masculino , Antioxidantes/metabolismo , Espermatozoides/metabolismo , Motilidad Espermática , Semen/metabolismo , Estrés Oxidativo , Infertilidad Masculina/inducido químicamente , CobaltoRESUMEN
(1) Background: The involvement of redox balance alterations and innate immunity is suggested to play a key role in the pathogenesis of sarcopenia. This investigation aimed to define and relate modifications in circulating markers of redox homeostasis and the innate immune response in human sarcopenia. (2) Methods: A total of 32 subjects aged >65 years old and affected by sarcopenia according to the second "European Working Group on sarcopenia in older people" guidelines were compared with 40 non-sarcopenic age-matched controls. To assess systemic redox homeostasis, reduced (GSH) and oxidized (GSSG) blood glutathione and plasma malondialdehyde (MDA)- and 4-hydroxy-2,3-nonenal (HNE)-protein adducts were measured. Immune cells and circulating interleukins were determined to compare the innate immune response between both groups. (3) Results: Impaired redox balance in sarcopenic patients, characterized by a high blood GSSG/GSH ratio and plasma MDA/HNE-protein adducts, was sustained by reduced antioxidants in peripheral blood mononuclear cells. Furthermore, sarcopenic patients showed higher neutrophil-to-lymphocyte ratios and interleukin (IL)-4, IL-6, IL-10, and tumor necrosis factor (TNF) with respect to non-sarcopenic patients. Linear regression analysis resulted in a strong association between redox balance and immune response markers in the sarcopenic group. (4) Conclusions: These results support the interplay between redox homeostasis alteration and disruption of the innate immune response in the pathogenesis of sarcopenia.
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Introduction: Oxidative stress is one of many factors suspected to promote antinuclear autoantibody (ANA) formation. Reactive oxygen species can induce changes in the antigenic structure of macromolecules, causing the immune system to treat them as "neo-antigens" and start production of autoantibodies. This study was designed to evaluate the relationship between oxidative stress markers, lifestyle factors and the detection of ANA. Material and methods: We examined measures of oxidative stress indices of free-radical damage to lipids and proteins, such as total oxidant status (TOS), concentration of protein thiol groups (PSH), and malondialdehyde (MDA), activity of superoxide dismutase (SOD) in 1731 serum samples. The parameters of the non-enzymatic antioxidant system, such as total antioxidant status (TAS) and uric acid (UA) concentration, were also measured and the oxidative stress index (OSI-index) was calculated. All samples were tested for the presence of ANA using an indirect immunofluorescence assay (IIFA). Results: The presence of ANA in women was associated with lower physical activity (p = 0.036), less frequent smoking (p = 0.007) and drinking of alcohol (p = 0.024) accompanied by significant changes in SOD isoenzymes activity (p < 0.001) and a higher uric acid (UA) concentration (p < 0.001). In ANA positive males we observed lower concentrations of PSH (p = 0.046) and increased concentrations of MDA (p = 0.047). Conclusions: The results indicate that local oxidative stress may be associated with increased probability of ANA formation in a sex-specific manner.
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BACKGROUND: Mechanisms underpinning ARDS induced by COVID-19 are mostly immune-mediated, but need to be completely clarified. This study aimed to investigate redox balance in COVID-19 patients with ARDS, trying to recognize possible differences from typical ARDS related to the pathophysiology of severe disease. METHODS: Patients affected by ARDS and positive for the SARS-CoV-2 virus (N = 40, COVID-19) were compared to ARDS patients negative to the molecular test (N = 42, No COVID-19). Circulating markers of redox balance were measured in serum and erythrocytes, and related to markers of inflammation and coagulability. RESULTS: No differences in serum markers of oxidative damage were found between both groups, but a reduction in total antioxidant status and serum ceruloplasmin level was observed in COVID-19 rather than No COVID-19 patients. Redox balance alterations were described in erythrocytes from COVID-19 with respect to No COVID-19 group, characterized by increased lipofuscin and malondialdehyde concentration, and reduced glutathione S-transferase and glutathione reductase activity. These markers were associated with circulating indexes of respiratory disease severity (Horowitz index and alveolar-to-arterial oxygen gradient), inflammation (interleukin-6 and interleukin-10), and hypercoagulability (D-dimer) in COVID-19 patients with ARDS. CONCLUSIONS: ARDS caused by COVID-19 is sustained by impairment of redox balance, particularly in erythrocytes. This alteration is associated with the pro-inflammatory and pro-coagulant status which characterizes severe COVID-19.
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Heavy metal poisoning can have serious health consequences, including damage to the brain, kidneys, and other organs. Cadmium is a toxic heavy metal that can accumulate in the body over time and the exposure to this element has been linked to a variety of adverse health effects. Cadmium toxicity can lead to an imbalance in the cellular redox state and be a source of oxidative stress. On the molecular level, cadmium ions negatively affect cellular metabolism, including the disruption of energy production, protein synthesis, and DNA damage. The study has been carried out on a group of 140 school-age children (8 to 14 years old) inhabiting the industrialized areas of Upper Silesia. The study population was divided into two sub-groups based on the median concentration of cadmium in blood (0.27 µg/L): Low-CdB and High-CdB. Measured traits comprised blood cadmium levels (CdB) as well as a blood count and selected oxidative stress markers. This research study aimed to demonstrate a correlation between the impact of exposure to elevated cadmium concentrations in a population of children and certain markers of oxidative stress, and 25-OH vitamin D3 concentration. A negative correlation has been found between cadmium concentration and 25-OH vitamin D3 level, protein sulfhydryl groups content in blood serum, glutathione reductase activity, and lipofuscin and malondialdehyde levels in erythrocytes. The concentration of 25-OH vitamin D3 in the High-CdB group was decreased by 23%. The oxidative stress indices can be considered a valuable indicator of early Cd-toxicity effects to be included in the routinely-applied cadmium exposure monitoring parameters, allowing the evaluation of stress intensity to the cell metabolism.
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Redox homeostasis is determinant in the modulation of quiescence/self-renewal/differentiation of stem cell lines. The aim of this study consisted of defining the impact of redox modifications on cell fate in a human hepatic progenitor line. To achieve this, the HepaRG cell line, which shows oval ductular bipotent characteristics, was used. The impact of redox status on the balance between self-renewal and differentiation of HepaRG cells was investigated using different methodological approaches. A bioinformatic analysis initially proved that the trans-differentiation of HepaRG toward bipotent progenitors is associated with changes in redox metabolism. We then exposed confluent HepaRG (intermediate differentiation phase) to oxidized (H2O2) or reduced (N-acetylcysteine) extracellular environments, observing that oxidation promotes the acquisition of a mature HepaRG phenotype, while a reduced culture medium stimulates de-differentiation. These results were finally confirmed through pharmacological modulation of the nuclear factor (erythroid-derived 2)-like 2 (NRF2), a principal modulator of the antioxidant response, in confluent HepaRG. NRF2 inhibition led to intracellular pro-oxidative status and HepaRG differentiation, while its activation was associated with low levels of reactive species and de-differentiation. In conclusion, this study shows that both intra- and extracellular redox balance are crucial in the determination of HepaRG fate. The impact of redox status in the differentiation potential of HepaRG cells is significant on the utilization of this cell line in pre-clinical studies.
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Peróxido de Hidrógeno , Factor 2 Relacionado con NF-E2 , Humanos , Factor 2 Relacionado con NF-E2/metabolismo , Peróxido de Hidrógeno/metabolismo , Hígado/metabolismo , Línea Celular , Células Madre/metabolismo , Diferenciación Celular/fisiología , Oxidación-Reducción , Hepatocitos/metabolismoRESUMEN
This study attempts to determine whether the increased blood lead concentration affects the posturographic test and to determine the relationship between the parameters of posture stability and selected parameters of oxidative stress. The study population consisted of 268 male employees and was divided into two equal subgroups, depending on the lead content in the blood. A posturographic examination was performed. Concentrations of lead, cadmium, zinc protoporphyrin, selected essential elements, and selected markers of oxidative stress in the blood were tested. Higher blood lead concentrations positively affected the values of the sway results: the field and the mean velocity of the center of the feet pressure in posturography. The absolute value of the proprioception ratio was similar in both subgroups. The content of malondialdehyde shows a statistically significantly higher value in a subgroup with high blood lead concentration and exhibits significant correlations only with some of the posturography parameters. The lipofuscin content in erythrocytes correlates with the results of the posturography test. Zinc protoporphyrin, total oxidant status, total antioxidant capacity, selected minerals, and metals did not correlate with the results of the posturography test. In conclusion, posturographic results correlate only with selected markers of oxidative stress, so it can be assumed that the effect on the body balance is only partial.
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Plomo , Postura , Humanos , Masculino , Propiocepción , Estrés Oxidativo , EritrocitosRESUMEN
BACKGROUND: Sodium glucose cotransporter-2 inhibitors (SGLT2-I) are the most recently approved drugs for type 2 diabetes (T2D). Recent clinical trials of these compounds reported beneficial cardiovascular (CV) and renal outcomes. A major cause of vascular dysfunction and CV disease in diabetes is hyperglycemia associated with inflammation and oxidative stress. Pre-clinical studies demonstrated that SGLT2-I reduce glucotoxicity and promote anti-inflammatory effects by lowering oxidative stress. AIM: To investigate the effects of SGLT2-I on markers of oxidative stress, inflammation, liver steatosis, and fibrosis in patients of T2D with non-alcoholic fatty liver disease (NAFLD). METHODS: We referred fifty-two consecutive outpatients treated with metformin monotherapy and exhibiting poor glycemic control to our centre. We introduced the outpatients to an SGLT2-I (dapagliflozin, empagliflozin, or canagliflozin; n = 26) or a different hypoglycemic drug [other glucose-lowering drugs (OTHER), n = 26]. We evaluated circulating interleukins and serum hydroxynonenal (HNE)- or malondialdehyde (MDA)-protein adducts, fatty liver index (FLI), NAFLD fibrosis score, aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio, AST-to-platelet-ratio index (APRI), and fibrosis-4 on the day before (T0) and following treatment for six months (T1). We also performed transient elastography at T0 and T1. RESULTS: Add-on therapy resulted in improved glycemic control and reduced fasting blood glucose in both groups. Of note, following treatment for six months, a reduction of FLI and APRI, as well as of the FibroScan result, was reported in patients treated with SGLT2-I, but not in the OTHER group; furthermore, in the SGLT2-I group, we reported lower circulating levels of interleukin (IL)-1ß, IL-6, tumor necrosis factor, vascular endothelial growth factor, and monocyte chemoattractant protein-1, and higher levels of IL-4 and IL-10. We did not observe any modification in circulating interleukins in the OTHER group. Finally, serum HNE- and MDA-protein adducts decreased significantly in SGLT2-I rather than OTHER patients and correlated with liver steatosis and fibrosis scores. CONCLUSION: The present data indicate that treatment with SGLT2-I in patients with T2D and NAFLD is associated with improvement of liver steatosis and fibrosis markers and circulating pro-inflammatory and redox status, more than optimizing glycemic control.
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Diabetes Mellitus Tipo 2 , Hepatitis , Enfermedad del Hígado Graso no Alcohólico , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hepatitis/complicaciones , Humanos , Hipoglucemiantes/uso terapéutico , Inflamación/complicaciones , Inflamación/tratamiento farmacológico , Cirrosis Hepática/complicaciones , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Oxidación-Reducción , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
Introduction: Cardiovascular disease (CVD) is a major cause of morbidity and mortality throughout the world. The LIPIDOGRAM2015 study was performed to estimate the prevalence of risk factors for atherosclerotic diseases as well as cardiovascular and related disorders in the primary care setting in Poland. The LIPIDOGEN2015 sub-study was designed to include a random cohort of patients in order to analyse parameters related to lipid metabolism, oxidative stress, inflammatory responses, autoimmune disorders, and gene variants that confer susceptibility to cardiometabolic and atherosclerotic diseases. Material and methods: The recruitment was carried out by 438 primary care physicians in Poland. The expected number of patients recruited for the LIPIDOGRAM2015 study was 13,000-14,000 with 13-15% (1700-2000) also participating in the LIPIDOGEN2015 sub-study. Each patient had to complete a questionnaire concerning medical and family history, concomitant diseases, and pharmacotherapy. Anthropometric measurements were performed at the doctor's office. For the LIPIDOGEN2015 sub-study, saliva samples for DNA isolation and blood samples for measurement of glycated haemoglobin, oxidative stress parameters, autoantibody levels, and inflammatory cytokine profile and apolipoprotein profile were collected. Follow-up data will be obtained from the National Health Fund in Poland. Results: The LIPIDOGRAM2015 and LIPIDOGEN2015 study cohort reflects the prevalence of cardiovascular risk factors and concomitant diseases, markers of oxidative stress, the presence of autoantibodies, inflammatory cytokine profile, and apolipoprotein profile, as well as genetic variants potentially conferring susceptibility to cardiometabolic and atherosclerotic diseases. Conclusions: This study presents the prevalence of different CV risk factors, with special emphasis on lipid disorders, and it assesses the relationship between inflammation, oxidative stress, and mutations in genes encoding proteins regulating lipid metabolism, as well as genes conferring susceptibility to cardiovascular, cardiometabolic, and related diseases.
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BACKGROUND: The anti-DFS70 autoantibodies are one of the most commonly and widely described agent of unknown clinical significance, frequently detected in healthy individuals. It is not known whether the DFS70 autoantibodies are protective or pathogenic. One of the factors suspected of inducing the formation of anti-DFS70 antibodies is increased oxidative stress. We evaluated the coexistence of anti-DFS70 antibodies with selected markers of oxidative stress and investigated whether these antibodies could be considered as indirect markers of oxidative stress. METHODS: The intensity of oxidative stress was measured in all samples via indices of free-radical damage to lipids and proteins such as total oxidant status (TOS), concentrations of lipid hydroperoxides (LPH), lipofuscin (LPS), and malondialdehyde (MDA). The parameters of the non-enzymatic antioxidant system, such as total antioxidant status (TAS) and uric acid concentration (UA), were also measured, as well as the activity of superoxide dismutase (SOD). Based on TOS and TAS values, the oxidative stress index (OSI) was calculated. All samples were also tested with indirect immunofluorescence assay (IFA) and 357 samples were selected for direct monospecific anti DFS70 enzyme-linked immunosorbent assay (ELISA) testing. RESULTS: The anti-DFS70 antibodies were confirmed by ELISA test in 21.29% of samples. Compared with anti-DFS70 negative samples we observed 23% lower concentration of LPH (P = .038) and 11% lower concentration of UA (P = .005). TOS was 20% lower (P = .014). The activity of SOD was up to 5% higher (P = .037). The Pearson correlation showed weak negative correlation for LPH, UA, and TOS and a weak positive correlation for SOD activity. CONCLUSION: In samples positive for the anti-DFS70 antibody a decreased level of oxidative stress was observed, especially in the case of samples with a high antibody titer. Anti-DFS70 antibodies can be considered as an indirect marker of reduced oxidative stress or a marker indicating the recent intensification of antioxidant processes.
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The detection of antinuclear autoantibody (ANA) is dependent on many factors and varies between the populations. The aim of the study was first to assess the prevalence of ANA in the Polish adult population depending on age, sex and the cutoff threshold used for the results obtained. Second, we estimated the occurrence of individual types of ANA-staining patterns. We tested 1731 patient samples using commercially available IIFA using two cutoff thresholds of 1:100 and 1:160. We found ANA in 260 participants (15.0%), but the percentage of positive results strongly depended on the cutoff level. For a cutoff threshold 1:100, the positive population was 19.5% and for the 1:160 cutoff threshold, it was 11.7%. The most prevalent ANA-staining pattern was AC-2 Dense Fine speckled (50%), followed by AC-21 Reticular/AMA (14.38%) ANA more common in women (72%); 64% of ANA-positive patients were over 50 years of age. ANA prevalence in the Polish population is at a level observed in other highly developed countries and is more prevalent in women and elderly individuals. To reduce the number of positive results released, we suggest that Polish laboratories should set 1:160 as the cutoff threshold.
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Anticuerpos Antinucleares/sangre , Enfermedades Autoinmunes/inmunología , Adulto , Factores de Edad , Enfermedades Autoinmunes/sangre , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Polonia , Factores SexualesRESUMEN
Lead-exposure is known to disrupt the redox balance of tissues leading to oxidative stress. Due to the fact that a mucolytic drug, erdosteine, exerts also antioxidant properties, we decided to perform a pilot study on rats to evaluate its therapeutic potency in lead poisoning. Male Wistar rats were divided randomly into the following seven groups having 10 animals in each. Group I served as the control group. During 8-week period, rats in groups II-IV, except standard alimentation, received: erdosteine in a dose 350 mg/kg (collateral control group), 1200 ppm of lead acetate in drinking water and placebo, as well as the same doses of lead and erdosteine, respectively. Rats in group V-VII received 1200 ppm of lead acetate in drinking water for the initial 6-week period and then administered: placebo, erdosteine and EDTA for 2 weeks, respectively. The levels of malondialdehyde (MDA) were significantly higher in groups III and V compared to the control group. The activities of catalase (CAT) were significantly higher in groups IV, V, and VI compared to the control group. The activities of glutathione-S-transferase (GST) were significantly lower in group II and significantly higher in groups VI and VII compared to the control group, while the activities of glutathione reductase (GR) were significantly lower in group III and significantly higher in group VI. Erdosteine has an effect of protection against lead-induced oxidative stress which is not worse than that of EDTA.
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Plomo , Estrés Oxidativo , Animales , Antioxidantes/metabolismo , Antioxidantes/farmacología , Catalasa/metabolismo , Masculino , Malondialdehído , Músculos/metabolismo , Proyectos Piloto , Ratas , Ratas Wistar , Superóxido Dismutasa/metabolismo , Tioglicolatos , TiofenosRESUMEN
Lead (Pb) is a toxic heavy metal ubiquitously distributed around the world, especially in industrial areas. Occupational and environmental exposures to Pb have detrimental effects on human health. Pb affects functioning of many systems of the human body, including the cardiovascular system. Angiogenesis, the process of new blood vessel formation, which makes critical contribution throughout life is deranged in various diseases. Excessive angiogenesis may result in different diseases including cancer. On the other spectrum, insufficient angiogenesis is observed in many diseases, such as atherosclerosis, hypertension, and cardiovascular disease. These disorders are also associated with occupational Pb exposure. In this paper, epidemiological and experimental studies are reviewed selectively for evidence in support of this hypothesis, that is, interactions between Pb and angiogenesis. We discuss the evidence for the possible mechanism of Pb impact on concentrations of angiogenic factors. Studies suggested that Pb exposure affects the level of angiogenic factors associated with angiogenesis regulation and promotion. Further research is needed, especially in the mechanisms in which Pb-induced vascular endothelial growth factor (VEGF) disregulation is present. We believe that characterizing the connection between Pb and angiogenesis will provide helpful information for the development of intervention strategies to reduce the adverse effects of Pb exposure.
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Neoplasias , Factor A de Crecimiento Endotelial Vascular , Humanos , Plomo/toxicidad , Neovascularización Patológica/inducido químicamente , Factor A de Crecimiento Endotelial Vascular/metabolismo , Factores de Crecimiento Endotelial VascularRESUMEN
Environmental factors may negatively contribute to a progressive worsening of semen quality, and differences in semen quality may result from different environmental exposures (regional differences) or lifestyle differences. Heavy metals are factors with a confirmed negative influence on male fertility. Among them, lead and cadmium are commonly found in human surroundings. Thus, we analyzed semen parameters (according to the World Health Organization 2010 recommendations) and semen lead and cadmium concentrations in 188 men from two different regions in Poland, a typical agricultural area and an industrial area, in couples that had been diagnosed with infertility. The assays were performed using flameless electrothermal atomic absorption spectrometry. In the statistical analysis, regional comparisons and then taxonomic comparisons based on three parameters (age, semen concentration, and sperm morphology) were applied. We showed that more cadmium than lead accumulated in semen, a higher cadmium concentration was observed in semen obtained from men from the agricultural region, and better semen quality and lower cadmium concentrations were found in the semen of men from the industrial, more polluted region. We thus showed an existing regionalism in the sperm quality properties. However, semen parameters such as morphology and progressive and nonprogressive motility followed the same trends, regardless of the patient's age, region, or class. We could conclude that the environment has a minor impact on sperm morphology and progressive and nonprogressive motility and that other existing factors could have an indirect influence on semen quality.
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Cadmio , Infertilidad Masculina , Exposición a Riesgos Ambientales/efectos adversos , Exposición a Riesgos Ambientales/análisis , Humanos , Infertilidad Masculina/inducido químicamente , Masculino , Semen , Análisis de Semen , Recuento de Espermatozoides , Motilidad Espermática , EspermatozoidesRESUMEN
BACKGROUND: Senescence is characterized by a decline in hepatocyte function, with impairment of metabolism and regenerative capacity. Several models that duplicate liver functions in vitro are essential tools for studying drug metabolism, liver diseases, and organ regeneration. The human HepaRG cell line represents an effective model for the study of liver metabolism and hepatic progenitors. However, the impact of senescence on HepaRG cells is not yet known. AIM: To characterize the effects of senescence on the transdifferentiation capacity and mitochondrial metabolism of human HepaRG cells. METHODS: We compared the transdifferentiation capacity of cells over 10 (passage 10 [P10]) vs P20. Aging was evaluated by senescence-associated (SA) beta-galactosidase activity and the comet assay. HepaRG transdifferentiation was analyzed by confocal microscopy and flow cytometry (expression of cluster of differentiation 49a [CD49a], CD49f, CD184, epithelial cell adhesion molecule [EpCAM], and cytokeratin 19 [CK19]), quantitative PCR analysis (expression of albumin, cytochrome P450 3A4 [CYP3A4], γ-glutamyl transpeptidase [γ-GT], and carcinoembryonic antigen [CEA]), and functional analyses (albumin secretion, CYP3A4, and γ-GT). Mitochondrial respiration and the ATP and nicotinamide adenine dinucleotide (NAD+)/NAD with hydrogen (NADH) content were also measured. RESULTS: SA ß-galactosidase staining was higher in P20 than P10 HepaRG cells; in parallel, the comet assay showed consistent DNA damage in P20 HepaRG cells. With respect to P10, P20 HepaRG cells exhibited a reduction of CD49a, CD49f, CD184, EpCAM, and CK19 after the induction of transdifferentiation. Furthermore, lower gene expression of albumin, CYP3A4, and γ-GT, as well as reduced albumin secretion capacity, CYP3A4, and γ-GT activity were reported in transdifferentiated P20 compared to P10 cells. By contrast, the gene expression level of CEA was not reduced by transdifferentiation in P20 cells. Of note, both cellular and mitochondrial oxygen consumption was lower in P20 than in P10 transdifferentiated cells. Finally, both ATP and NAD+/NADH were depleted in P20 cells with respect to P10 cells. CONCLUSION: SA mitochondrial dysfunction may limit the transdifferentiation potential of HepaRG cells, with consequent impairment of metabolic and regenerative properties, which may alter applications in basic studies.
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BACKGROUND: The emission of lead (Pb) occurring during the extraction, processing and industrial applications of this element remains a significant environmental risk factor. The absorbability of lead in humans is strongly associated with the general health status of exposed individuals. Existing mineral deficiencies are considered being a predisposition to an increased Pb uptake. Both, iron deficiency and lead poisoning are the major causative factors responsible for the prevalence of anemia within the vulnerable population, especially in children. Although some of the intervention programs of counteracting lead poisoning by iron supplementation proved to be effective in the Pb-exposed population, the exact mechanisms of this interaction still require further studies. The objective of the presented study was to examine the association of iron level on oxidative stress measures and its effects on the severity of lead toxicity in the exposed population. METHODS: The analyzed population consisted of 270 male workers from the lead-zinc smelter. The studied population was divided into two sub-groups based on the serum iron concentration: low iron level group (L-Fe; Fe < median value) and high iron level group (H-Fe; Fe > median value). Measured traits comprised of blood lead (PbB), serum Fe and zinc protoporphyrin (ZPP) levels as well as a blood count and oxidative stress markers. RESULTS: No significant correlation between serum iron concentration and PbB in the tested cohort was found. On the contrary, the analysis of ZPP levels (long-term marker related to a hematologic toxic effect of Pb) within the subgroups differing in serum Fe level shown that ZPP was 12.3 % lower (p = 0.043) in subjects classified within the H-Fe group. A positive correlation of serum Fe and total antioxidant capacity (TAC) was found (R = 0.1999). The conducted 3-D PCA analysis showed that individuals classified within the H-Fe group were characterized by the co-occurrence of higher Fe levels, lower ZPP, and higher TAC value. CONCLUSION: These results support the existing evidence providing that maintaining the optimal status of Fe may play a significant role in preventing the lead poisoning and alleviating harmful effects of Pb on the oxidative balance in humans.
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Deficiencias de Hierro , Intoxicación por Plomo , Plomo/metabolismo , Estrés Oxidativo , Antioxidantes , Biomarcadores , Niño , Humanos , Hierro , MasculinoRESUMEN
Safety of healthcare workers in hospitals is a major concern during the COVID-19 pandemic. Being exposed for several working hours per day to infected patients, nurses dealing with COVID-19 face several issues that lead to physical/psychological breakdown. This study focused on burnout and its associated factors in nurses working in an Italian University Hospital during the first wave of COVID-19 pandemic. We designed a web-based cross-sectional study addressed to nurses working at the University Hospital in Foggia, Italy. The online questionnaire was organized in sections aimed at collecting demographic and occupational variables, including the Maslach Burnout Inventory (MBI) and the Oldenburg Burnout Inventory (OBI). Two hundred and ninety-three nurses agreed to participate. According to MBI, we reported moderate/high emotional exhaustion in 76.5%, depersonalization in 50.2%, and personal gratification in 54.6% of participants. COVID-19-related burnout measured by OBI resulted medium/high in 89.1% of participants. Among demographic and occupational factors, a multivariate regression analysis identified emotional support, consideration of leaving job, and workload as predictive of burnout in nurses. In conclusion, this study suggests that the improvement of employer and family support to nurses, as well as reduction of workload and job-related stress, would contribute to reducing burnout in nurses during COVID-19 pandemics.
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Agotamiento Profesional , COVID-19 , Enfermeras y Enfermeros , Agotamiento Profesional/epidemiología , Agotamiento Psicológico , Estudios Transversales , Hospitales Universitarios , Humanos , Italia/epidemiología , Pandemias , SARS-CoV-2 , Encuestas y CuestionariosRESUMEN
Occupational exposure to lead is one of the important hazards to human global population. Lead interferes with divalent cations, such as calcium, magnesium, and iron. Magnesium is the fourth most common mineral in the human body and a cofactor in more than 325 enzymes. There are many disorders associated with magnesium deficiency. It has been postulated that hypomagnesemia promotes oxidative stress. Study population included 232 male employees of lead-zinc works and was divided into two sub-groups based on the median of magnesium serum level: low magnesium level (L-Mg) group and high magnesium level (H-Mg) group. Magnesium level was significantly higher in the H-Mg group than in the L-Mg group due to the study design. The level of zinc protoporphyrin was significantly higher in the L-Mg group than in the H-Mg group by 13%, while the blood lead levels were similar in the examined groups. The serum level of MDA was significantly higher in the L-Mg group than in the H-Mg group by 12%, while the serum levels of thiol groups, TAC, and bilirubin were significantly lower in that group by 6%, 3%, and 27%, respectively. Similarly, the erythrocyte SOD activity was lower in the L-Mg group than in the H-Mg group by 5%. Low serum magnesium levels contribute to lead-induced oxidative stress, result in unfavorable modification of antioxidant system function, and promote lead-induced impairment of heme synthesis. Obtained results indicate that prevention of hypomagnesemia should be regarded as an important step in ensuring adequate prophylaxis of chronic lead poisoning.