Click evoked otoacoustic emissions in occupational exposure to lead, concentrations of selected essential elements and markers of oxidative stress.

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.

Redox-Dependent Modulation of Human Liver Progenitor Cell Line Fate.

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.

Metal-on-metal metaphyseal and ceramic-on-ceramic femoral neck arthroplasty: the impact on clinical results, oxidative stress and concentration of metal ions in serum and blood.

PURPOSE: Growing number of hip arthroplasty in Poland performed with the use of metaphyseal stems results from the decreasing age of patients qualified for procedures and is consistent with the corresponding trends in European countries. To this day, a significant population functions after undergoing hip replacement using metal-on-metal implant. This study was aimed at the assessment of the variability of the oxidative system, as well as the concentrations of chromium and cobalt ions in serum and blood and their potential impact on postoperative clinical status. MATERIAL AND METHODS: The analysis included 58 men. The first group-operated using J&J DePuy ASR metal-on-metal implant with metaphyseal stem ProximaTm. Second group-operated using K-Implant SPIRON® femoral neck prosthesis in full ceramic articulation. Selected parameters of oxidative stress and the antioxidant system as well as the concentration of metal ions in blood were determined twice. Each patient underwent two clinical evaluations using acclaimed physical examination scale systems. RESULTS: In the first group, significantly higher concentrations of Cr (p = 0.028) and Co (p = 0.002) were demonstrated compared to the group of femoral neck arthroplasty. The mean concentrations of Cr and Co, 10.45 and 9.26 µg/l, respectively, were higher in patients operated bilaterally. In the ASR group, greater pain intensity in the operated hip and higher indicators of oxidative stress were found. CONCLUSIONS: Metal-on-metal articulation of the hip significantly increases the concentration of Cr and Co in blood, induces oxidative stress and modifies function of the antioxidant system and generates greater pain in the operated hip.

Effects of environmental and occupational lead toxicity and its association with iron metabolism.

BACKGROUND: Discrepancies are present in the findings from clinical trials evaluating a physiological role of iron status in the lead-exposed population. OBJECTIVE: The purpose of this article was to summarize the current understanding of cellular mechanisms of lead toxicity and present a comprehensive review of existing clinical trials related to associations of lead poisoning and iron status. Although an association of iron metabolism pathways that are affected by lead intoxication has been studied, there are still aspects that remain to be elucidated. The existence of additional Pb uptake pathways besides DMT1 transporter-mediated is postulated to non-specifically regulate lead absorption. METHODS: Authors performed a systematic search of PubMed, EMBASE® and Web of Science databases to identify studies that reported an association between health risks of non-organic lead that are associated with iron status markers as possible effect modifier. RESULTS: There were 58 studies that met the pre-defined inclusion criteria for the systematic review. There is a strong body of evidence supporting the hypothesis that alleviated blood lead level can be correlated with a reduced body iron store and increasing the risk of anemia. This association is of a high significance in cases of a young adolescent, weaker in groups of older children and often without a statistical significance in adults. DISCUSSION: Discrepancies in the observations may result from different specificities of lead absorption pathways in children and adults, as well as the power of the statistical tests in varying population sizes. It may be assumed that the extent of iron deficits coupled together with source, timing, and severity of lead exposure, significantly influence the correlation between these factors. Some of the intervention programs of counteracting lead poisoning by iron supplementation proved to be effective and may be a promising prevention strategy for the exposed population.

Antioxidant System and Ions Concentrations After Femoral Neck and Resurfacing Hip Arthroplasty.

BACKGROUND Oxidative stress is a disruption of the pro-oxidative-antioxidant balance, caused by excessive production or ineffective removal of reactive oxygen species. MATERIAL AND METHODS The study included 42 male patients aged 38 to 69 years. The first group consisted of 21 men with osteoarthritis after primary hip arthroplasty using the Smith & Nephew Birmingham Hip Resurfacing implant. The second group included 21 men after hip arthroplasty using the femoral neck SPIRON K-implant. In both groups, concentrations of ions, the antioxidant system in the blood, and parameters of oxidative stress were evaluated twice. Clinical assessment using the Western Ontario and McMaster Universities Osteoarthritis Index, Harris Hip Score, and Short Form (12) Health Survey (SF-12) scales was performed. RESULTS Concentrations of metal ions in the blood and the level of oxidative stress were significantly higher in the resurfacing group than in the femoral neck arthroplasty group. The response of the antioxidant system was significantly greater in the femoral neck arthroplasty group. During clinical evaluation, groups did not show significant differences, with the exception of greater shortening of the operated limb and a lower score in the mental-sphere of the SF-12 scale in the resurfacing arthroplasty group. CONCLUSIONS Resurfacing hip arthroplasty increased oxidative stress, increased the concentration of metal ions, and did not affect alignment of the abbreviation of the operated limb. A significant improvement in the quality of life of patients in the mental sphere according to the SF-12 occurred after the application of resurfacing arthroplasty, in the first month after the procedure.

Analysis of the impact of sex and age on the variation in the prevalence of antinuclear autoantibodies in Polish population: a nationwide observational, cross-sectional study.

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.

Angiogenesis and lead (Pb): is there a connection?

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.

The influence of erdosteine administration on lead-induced oxidative stress in rat muscle.

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.

Relationship between Postural Stability, Lead Content, and Selected Parameters of Oxidative Stress.

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.

Validation of the test for detecting SARS--CoV-2 antigens in the Polish population in patients with suspected SARS-CoV-2 infection.

In December 2019, the World Health Organization (WHO) reported that China had accumulated pneumonia of unclear etiology in Wuhan. According to WHO recommendations, in strictly defined situations, antigen tests can be implemented into the diagnostic algorithm to reduce the number of molecular tests performed and support the rapid identification and treatment of COVID-19 patients. According to WHO recommendations, the antigen test for diagnostic use should have a sensitivity of ≥ 80% and a specificity of ≥ 97% compared to molecular tests (NAAT). Based on the comparative analysis, the sensitivity and specificity of the SARS-CoV-2 Antigen ELISA test were determined concerning the RT-PCR reference method. The sensitivity of the SARS-CoV-2 Antigen ELISA was 100% (51/51) and the specificity was 98.84%. The obtained data demonstrate that the analyzed antigen test meets both the WHO and the Ministry of Health criteria.

THE INFLUENCE OF HIP ARTHROPLASTY ON HEALTH RELATED QUALITY OF LIFE IN MALE POPULATION WITH OSTEOARTHRITIS HIP DISEASE.

OBJECTIVE: Introduction: Hip osteoarthritis is a disabling disease which become substantial health-related, social, and economic issue. The aim: To assess short term quality of life in male population with hip ostheoarthritis, after total hip arthroplasty. PATIENTS AND METHODS: Material and methods: 118 male patients were included in the study, age range from 31 to 79 year-old, who underwent total hip arthroplasty. Patients quality of life was assessed using questioners: abbreviated version of WHOQoL-BREF, as well as EQ-5D-5L, and SF-36 scale. Patients condition was investigated before surgery, 6 weeks and 6 months after the surgery. RESULTS: Results: The results from WHOQoL-BREF questionnaire demonstrated a statistically significant improvement of quality of life after the surgery - 6 weeks after the procedure by 4% and 21% (p<0.001), after 6 months by 13% and 42% (p<0.001), respectively. The most significant improvement was found in the somatic domain - by 5% after 6 weeks, and by 6% after 6 months (p<0.001). The quality of life according to the EQ-5D-5L questionnaire revealed statistically significant improvement after 6 weeks, by 18-24% (p<0.001), after 6 months by 41-48% (p<0.001). Substantial improvement was achieved in reducing pain and improving mobility. SF-36 questionnaire showed statistically significant improvement after 6 months from the surgery in both physical (by 44%), and mental condition (by 54%) (p<0.001). CONCLUSION: Conclusions: Improvement of the quality of life - mainly less severe pain and better mobility after total hip arthroplasty in the investigated group of men was proven in 6 weeks after the procedure, while the further progress was more noticeable 6 months after the procedure.

Effect of Total Ankle Arthroplasty and Ankle Arthrodesis for Ankle Osteoarthritis: A Comparative Study.

BACKGROUND Surgical methods in treatment of joint osteoarthritis (OA) aim at meeting the increasing expectations of people with active lifestyles. Ankle joint arthroplasty has been performed increasingly more often as an alternative to arthrodesis. The aim of this study was to compare arthrodesis and arthroplasty in the treatment of ankle osteoarthritis. MATERIAL AND METHODS The study involved 56 patients (45 males and 11 females) aged 21-72 years (mean 51) presenting with end-stage ankle OA: 29 patients (52%) underwent arthroplasty (Group A) and 27 patients (48%) underwent arthrodesis (Group B). Patients underwent surgery between 2004 and 2016 at a single clinical center. The observation period ranged from 6 to 150 months (mean 55 months). To assess the results of surgical treatment, quality of life (Health Assessment Questionnaire-HAQ, 12-Item Short-Form Survey-SF-12) and functional (American Orthopedic Foot & Ankle-AOFAS, Kofoed, Takakura) scores were used. For pain assessment, Visual Analog Scale was used (VAS). RESULTS After the surgery, group A and B had a statistically significant improvement in the joint function and pain relief according to AOFAS (A: 32.6 to 68.2; B: 27.4 to 61.3), Kofoed (A: 31.8 to 68; B: 25.9 to 60.3), Takakura (A: 30.6 to 62.9; B: 25.4 to 49.3), and VAS scores (A: 7.28 to 4.14; B: 7.33 to 3.78) compared with preoperative scores. After the surgery, quality of life scores improved in both groups, for HAQ (A: 0.91 to 0.53; B: 1.34 to 0.56) and for SF-12 (A: 26.6 to 36.8; B: 25.6 to 38.0). CONCLUSIONS The comparison of total ankle arthroplasty and ankle arthrodesis in treatment of end-stage ankle osteoarthritis did not reveal any significant differences.

The effect of occupational chronic lead exposure on the complete blood count and the levels of selected hematopoietic cytokines.

Associations among lead exposure, blood morphology, and cytokines influencing hematopoiesis are still inconclusive. Therefore, the objective of the present study was to demonstrate whether workers chronically exposed to lead demonstrate changes in complete blood count (CBC) parameters associated with altered levels of selected cytokines influencing hematopoiesis. The study covered 80 male subjects employed in the zinc-lead works in Miasteczko Slaskie. The subjects were divided into two groups: control group (24 healthy administration workers without a history of occupational exposure to lead compounds) and lead exposed group (56 subjects exposed to lead compounds in their work environment). The values of HTC, MCV, MCH, RDW-CV, PDW, and LMR were significantly lower in the exposed group than in the controls by 3%, 5%, 3%, 4%, 15%, and 47%, respectively. However, the levels of MCHC and MPV were higher in the exposed group than in the controls by 3% and 11%, respectively. Analogically, the values of MXD and MXD% were also significantly higher by 118% and 70%, respectively. The concentration of IL-7 was significantly higher in the exposed group compared to the controls by 143%. In this study, chronic lead exposure in the occupational setting at levels <50 µg/dl does not affect RBC count and hemoglobin level but decreases MCV and hematocrit. Similarly, chronic lead toxicity does not affect WBC count but alters proportions of different types of leukocytes with significant increase of MXD count associated with elevated level of IL-7. Oppositely to a short-term lead exposure, chronic lead exposure elevates MPV and does not alter PLT count.

The association between occupational lead exposure and serum levels of selected soluble receptors.

The present study was designed to evaluate soluble receptors as potential targets for lead (Pb). Analyses included the serum levels of soluble Vascular Endothelial Growth Factor Receptors 2 (sVEGFR-2), soluble Epidermal Growth Factor Receptor (sEGFR), soluble Human Epidermal Growth Factor 2 (sHER-2/neu), and soluble Interleukin 6 Receptors (sIL-6R) in the groups of chronically and subchronically occupationally exposed workers. The first group consisted of 56 male workers chronically exposed to Pb. The second group (control) comprised 24 male administrative workers. The third group included 36 male workers exposed to Pb for 40 ± 3 days. Examined subjects were employed in the Pb-zinc works to perform periodic maintenance of blast furnaces and production lines. The serum levels of sHER-2/neu and sIL-6R were significantly lower in the group of workers chronically exposed to Pb compared to control values by 45% ( p < 0.05) and 44% ( p < 0.05), respectively. The values of sVEGFR-2 and sEGFR decreased after a subchronic exposure to Pb compared to baseline by 14% ( p < 0.05) and 21% ( p < 0.05), respectively. At the same time, the levels of sIL-6R also decreased by 14% ( p < 0.05). Results of the present study indicated that both chronic and subchronic occupational Pb exposures resulted in decreased levels of several soluble receptors (sVEGFR-2, sEGFR, sHER-2/neu, and sIL-6R), probably due to Pb-induced modulations of the transcription factors and metalloprotease activities, that are necessary for soluble receptor synthesis.

The analysis of blood lead levels changeability over the 5-year observation in workers occupationally exposed to lead.

The aim of the present study was to compare a group of workers with stable lead levels with a group of workers with fluctuating lead levels in terms of selected hematological, biochemical, and immunological parameters. The examined group included male workers occupationally exposed to lead. Blood lead (PbB) levels were measured every 3 months during the 5-year observation. Based on standard deviation of mean PbB levels, the examined population was divided into two groups: low level of fluctuation (L-SD) and high level of fluctuation (H-SD) groups. The mean and maximal PbB levels were significantly higher in the H-SD group than in the L-SD group by 9 and 22%, respectively. At the same time, the maximal level of zinc protoporphyrin (ZPP) and standard deviation of mean ZPP level were higher in the H-SD group by 29 and 55%, respectively. The maximal level of hemoglobin and white blood cell (WBC) count as well as standard deviation of the mean hemoglobin level and WBC count were higher in the H-SD group by 2, 8, 58, and 24%, respectively. The expression of nuclear factor kappa-B1 gene and telomerase reverse transcriptase gene was significantly greater in the H-SD group than in the L-SD group by 11 and 28%, respectively. Workers occupationally exposed to lead do not represent a homogenous population. Some present stable lead levels, whereas others have fluctuating lead levels. These fluctuations are related to secondary changes in ZPP and hemoglobin levels as well as WBC count.

Blood morphology and the levels of selected cytokines related to hematopoiesis in occupational short-term exposure to lead.

The aim of the study was to investigate the influence of a short-term exposure to lead on the blood morphology and the levels of selected cytokines related to hematopoiesis in occupationally exposed workers. The study population included 37 males occupationally exposed to lead for 36 to 44days. Their blood lead level raised from 10.7±7.67µg/dl at baseline to the level of 49.1±14.1µg/dl at the end of the study. The level of hemoglobin and values of MCH and MCHC were decreased due to a short-term exposure to lead by 2%, 2%, and 1%, respectively. The counts of WBC, LYM, and MXD increased significantly by 5%, 7%, and 35%. Similarly, the count of PLT increased by 7%, while PDW, MPV, and P-LCR decreased by 6%, 3%, and 9%, respectively. The levels of IL-7, G-CSF, HGF, PDGF AB/BB, SCF, and PECAM-1, decreased significantly by 30%, 33%, 8%, 30%, 25%, and 20%, respectively. A short-term occupational exposure to lead results in a decreased hemoglobin level and increased counts of WBC and PLT. Changes in counts and proportions of different types of leukocytes and decreased values of PLT indices, such as PDW, MPV, and P-LCR, due to the subacute lead-exposure may be associated with lead-induced decreased levels of cytokines related to hematopoiesis, including SCF, G-CSF, IL-7, and PDGF.

Association between subchronic and chronic lead exposure and levels of antioxidants and chemokines.

PURPOSE: This study aimed to compare the influence of lead on the non-enzymatic antioxidant defenses and the levels of chemokines in workers subchronically and chronically exposed to lead. METHODS: The study population was divided into three groups. The first group consisted of male workers subchronically exposed to lead for 40 ± 3.2 days, while the second group included male workers chronically exposed to lead. The third group was a control group. RESULTS: The levels of uric acid and bilirubin were significantly higher after a subchronic exposure to lead compared to the baseline by 22 and 35 %, respectively. Similarly, the values of total antioxidant capacity (TAC), total oxidant status (TOS), and oxidative stress index (OSI) increased by 15, 50, and 33 %, respectively. At the same time, the levels of thiol groups and albumin decreased by 5 and 8 %, respectively. Additionally, the levels of interleukin-8 (IL-8) and macrophage inflammatory protein-1ß (MIP-1ß) were significantly higher after a subchronic exposure to lead compared to the baseline by 34 and 20 %, respectively. Moreover, IL-8 level was significantly higher by 40 % in the group of workers chronically exposed to lead than in the control group, while the level of interferon gamma-induced protein-10 (IP-10) was significantly lower by 28 %. CONCLUSIONS: Similar to chronic lead exposure, subchronic exposure to lead is associated with elevated blood levels of uric acid and bilirubin in humans. This probably results in increased TAC value despite thiol depletion. However, the compensatory activation of non-enzymatic antioxidant defenses seems to be insufficient to protect against lead-induced oxidative stress, which may be additively enhanced by the pro-inflammatory action of chemokines, especially IL-8.

Telomere length, telomerase expression, and oxidative stress in lead smelters.

The negative health effects caused by lead (Pb) exposure are widely recognized; however, the molecular mechanisms remain unknown. The aim of this study was to assess the effect of occupational Pb exposure on telomere length and to investigate the potential mechanisms leading to telomere shortening. A cohort of 334 male Pb smelters (exposed group) and 60 age-adjusted males unexposed to Pb (control group) were examined. Assessments of relative telomere length (rTL) and telomerase reverse transcriptase (TERT) gene expression were performed using quantitative real-time polymerase chain reactions. Assessments of whole blood Pb (B-Pb) and whole blood cadmium (B-Cd) concentrations and serum selenium concentration (S-Se) were performed using graphite furnace atomic absorption spectrometry. We analyzed total oxidation status (TOS), lipid hydroperoxides (LHPs), malonylodialdehyde levels in serum (MDA) and in erythrocyte hemolysates (MDA-hgb), and 8-hydroxy-deoxy-guanosine (8-OHdG). The Pb-exposed group had higher B-Pb values and shorter rTL than the control group. The arithmetic mean values calculated for B-Pb were 33 µg/dL versus 2.2 µg/dL (p < 0.0001), and the rTL values were 0.928 and 1.126 relative units (p = 0.001), respectively, for the Pb-exposed and control groups. The rTL was found to gradually shorten in response to the increasing levels of Pb exposure. The Pb-exposed group also demonstrated a higher level of oxidative stress than the control group, which was indicated by increased TOS and MDA-hgb values. rTL was negatively associated with parameters that indicated increased oxidative stress, including TOS (Spearman's rank coefficient (rS) = -0.16; p < 0.01) and MDA-hgb (rS = -0.17; p < 0.001). No correlations were found between rTL and B-Cd and S-Se or smoking and MDA and LHP levels. Univariate analysis indicated that B-Pb was associated with decreased rTL (ß =-0.0041; p = 0.0063) and that the association between B-Pb and rTL remained significant, even when adjusting for age (ß = -0.0041; p = 0.0065) and in multivariable-adjusted model (ß = -0.0042; p = 0.0063). In conclusion, occupational Pb exposure resulted in decreased rTL and may represent a mechanism that contributes to Pb-related diseases.

Effect of N-acetylcysteine administration on homocysteine level, oxidative damage to proteins, and levels of iron (Fe) and Fe-related proteins in lead-exposed workers.

N-Acetylcysteine (NAC) could be included in protocols designed for the treatment of lead toxicity. Therefore, in this study, we decided to investigate the influence of NAC administration on homocysteine (Hcy) levels, oxidative damage to proteins, and the levels of iron (Fe), transferrin (TRF), and haptoglobin (HPG) in lead (Pb)-exposed workers. The examined population (n = 171) was composed of male employees who worked with Pb. They were randomized into four groups. Workers who were not administered any antioxidants, drugs, vitamins, or dietary supplements were classified as the reference group (n = 49). The remaining three groups consisted of workers who were treated orally with NAC at three different doses (1 × 200, 2 × 200, or 2 × 400 mg) for 12 weeks. After the treatment, blood Pb levels significantly decreased in the groups receiving NAC compared with the reference group. The protein concentration was not affected by NAC administration. In contrast, Hcy levels significantly decreased or showed a strong tendency toward lower values depending on the NAC dose. Levels of the protein carbonyl groups were significantly decreased in all of the groups receiving NAC. Conversely, glutamate dehydrogenase activity was significantly elevated in all of the groups receiving NAC, while the level of protein thiol groups was significantly elevated only in the group receiving 200 mg of NAC. Treatment with NAC did not significantly affect Fe and TRF levels, whereas HPG levels showed a tendency toward lower values. Treatment with NAC normalized the level of Hcy and decreased oxidative stress as measured by the protein carbonyl content; this effect occurred in a dose-dependent manner. Moreover, small doses of NAC elevated the levels of protein thiol groups. Therefore, NAC could be introduced as an alternative therapy for chronic Pb toxicity in humans.

Telomere length in children environmentally exposed to low-to-moderate levels of lead.

Shorter relative telomere length in peripheral blood is a risk marker for some types of cancers and cardiovascular diseases. Several environmental hazards appear to shorten telomeres, and this shortening may predispose individuals to disease. The aim of the present cross-sectional study was to assess the effect of environmental exposure to lead on relative telomere length (rTL) in children. A cohort of 99 8-year-old children was enrolled from 2007-2010. Blood lead concentrations (B-Pb) were measured by graphite furnace atomic absorption spectrometry, and blood rTL was measured by quantitative PCR. The geometric mean of B-Pb was 3.28 µg/dl (range: 0.90-14.2), and the geometric mean of rTL was 1.08 (range: 0.49-2.09). B-Pb was significantly inversely associated with rTL in the children (rS = -0.25, p = 0.013; in further analyses both log-transformed-univariate regression analysis ß = -0.13, p = 0.026, and R(2)adj 4%; and ß = -0.12, p = 0.056 when adjusting for mothers' smoking during pregnancy, Apgar score, mother's and father's ages at delivery, sex and mother's education, R(2)adj 12%, p = 0.011). The effect of lead remained significant in children without prenatal tobacco exposure (N = 87, rS = -0.24, p = 0.024; in further analyses, ß = -0.13, p = 0.029, and R(2)adj 4%). rTL was not affected by sex, the concentrations of other elements in the blood (i.e., cadmium and selenium concentrations), or oxidative injury parameters (total antioxidant status, 8-hydroxydeoxyguanosine and thiobarbituric acid-reactive substances). Lead exposure in childhood appears to be associated with shorter telomeres, which might contribute to diseases, such as cardiovascular disease. The inverse association between blood lead level and the telomeres in children emphasizes the importance of further reducing lead levels in the environment.