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.

Relationship between lead absorption and iron status and its association with oxidative stress markers in lead-exposed workers.

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.

Levels of Macro- and Trace Elements and Select Cytokines in the Semen of Infertile Men.

The current study evaluated levels of macro-/trace elements, select cytokines, and sperm quality, in the semen of men with abnormal spermograms. The study population of men with abnormal spermograms was divided into three groups, i.e., oligospermic, asthenozoospermic, and oligoasthenozoospermic. The control group was fertile men with normal semen parameters. Analyses showed that in comparison with that in the semen of the fertile men, levels of calcium, magnesium, and selenium were significantly lower in men with all three groups. Semen levels of zinc were significantly lower in men with asthenospermia as compared with that in control. GGT (gamma-glutamyltranspeptidase) activity in semen was significantly higher in men in any of the three states as compared with that seen in control semen. In contrast, semen ALT (alanine aminotransferase) activity was reduced in men with any of these abnormalities compared with that in the controls. Semen cholesterol levels were significantly lower in men with asthenospermia as compared with control semen. Of all the measured cytokines, only IL-5 levels were reduced in the semen of the men with any of the conditions as compared with control semen. The semen of infertile males is characterized by reduced levels of calcium, magnesium, and trace metals such as zinc and selenium. The study also indicated that measures of cholesterol and of GGT/ALT activities could serve as supplementary parameters indicative of semen quality. Further investigations are needed to clarify the role of the measured parameters in sperm physiology.

An open-label, single-center pilot study to test the effects of an amino acid mixture in older patients admitted to internal medicine wards.

OBJECTIVE: Older patients are frequently subjected to prolonged hospitalization and extended bed rest, with a negative effect on physical activity and caloric intake. This results in a consistent loss of muscle mass and function, which is associated with functional decline and high mortality. The aim of this study was to investigate the effect of 1 wk of oral amino acid (AA) supplementation in older patients subjected to low mobility during hospitalization. METHODS: Hospitalized older patients (69-87) were included in the control group (n = 50) or were administered 25 g of AA mixture (n = 44) twice daily throughout 7 d of low mobility. We collected data related to length of stay as primary outcome measure. In-hospital mortality, 90-d postdischarge mortality, 90-d postdischarge rehospitalization, and falls also were considered. Moreover, variations of anthropometric measures, body composition and muscle architecture/strength, circulating interleukins, and oxidative stress markers between the beginning and the end of the supplementation period were analyzed as secondary outcomes. RESULTS: Similar values were reported between the two groups regarding age (76.6 ± 6.8 versus 79 ± 7.2 y old), body weight (61.5 ± 14.3 versus 62.1 ± 16.1 kg), and body mass index (28.7 ± 4.15 versus 28.1 ± 3.62 kg/m2). Although no difference in terms of in-hospital, 90-d postdischarge, or overall mortality rate was observed between the two groups, a reduction in length of stay, 90-d postdischarge hospitalization, and falls was observed in the AA supplementation group rather than in controls. Furthermore, the AA mixture limited muscle architecture/strength impairment and circulating oxidative stress, which occurred during hospitalization-related bed rest. The latter data was associated with increased circulating levels of anti-inflammatory cytokines interleukin-4 and -10. CONCLUSIONS: These results suggest that the AA mixture limits several alterations associated with low mobility in older hospitalized patients, such as length of stay, 90-d postdischarge hospitalization, and falls, preventing the loss of muscle function, as well as the increase of circulating interleukins and oxidative stress markers.

Evaluation of ß-endorphin concentration, mood, and pain intensity in men with idiopathic hip osteoarthritis treated with variable magnetic field.

Osteoarthritis is the most frequently diagnosed disease of the musculoskeletal system. Growing number of patients waiting for surgical treatment and the possible negative consequences resulting from long-term pharmacological therapy lead to the search for non-pharmacological methods aimed at alleviating pain and reducing doses of analgesics, among them physical therapy with use of magnetic fields.The study involved 30 men aged 49 to 76 (mean age, 61.7 years) treated for idiopathic osteoarthritis of the hip joint. The subjects were divided into 2 groups (15 patients each) and underwent a cycle of magnetostimulation and magnetoledtherapy procedures, respectively. During the exposure cycle concentrations of ß-endorphin were assessed 3 times and the mood was assessed 2 times. In addition, the assessment of pain intensity and the dose of analgesic drugs was performed before and after the end of therapy.Statistically significant increase in plasma ß-endorphins concentration was observed in both groups of patients (magnetostimulation-P < .01 vs magnetoledtherapy-P < .001). In the assessment of mood of respondents, no statistically significant differences were found. Significant reduction in intensity of perceived pain was observed in both groups of patients (P < .05). In the group of patients who underwent magnetoledtherapy cycle, the analgesic drug use was significantly lower by 13% (P < .05) as compared with initial values, which was not noted in group of patients who underwent magnetostimulation procedures.The use of magnetic field therapy in the treatment of men with idiopathic osteoarthritis of hip joints causes a statistically significant increase in the concentration of plasma ß-endorphins resulting in statistically significant analgesic effect in both magnetostimulation and magnetoledtherapy treated groups of patients, with accompanying decrease of need for analgetic drugs in magnetoledtherapy group, but without any significant changes regarding the patient's mood.

α-Tocopherol supplementation and the oxidative stress, homocysteine, and antioxidants in lead exposure.

To investigate whether α-tocopherol supplementation in workers exposed to lead would reduce the oxidative stress intensity and decrease homocysteine level, the examined population was randomly divided into two groups. Workers in the first group (n = 49, reference group) were not administered any drugs. Workers in the second group (n = 34) were administered orally α-tocopherol, 200 mg per day for 12 weeks. The level of α-tocopherol significantly increased compared to the baseline and the reference group. The level of thiol groups significantly increased compared to the reference group. However, the levels of malondialdehyde and homocysteine did not significantly change. Animal studies suggest the ability of α-tocopherol administration to reverse adverse health effects of lead exposure, such as oxidative stress; however, the results of this study on humans do not confirm these protective effects.

The effects of α-tocopherol administration in chronically lead exposed workers.

The aim of the study was to investigate whether α-tocopherol supplementation for workers who are chronically exposed to lead would normalize/improve the values of parameters that are associated with the lead-induced oxidative stress. Study population included chronically lead exposed males who were divided into two groups. Workers in the first group (reference group) were not given any antioxidants, while workers in the second group (αT group) received supplementation with α-tocopherol. After treatment, the blood lead and leukocyte malondialdehyde levels decreased significantly in the αT group compared to the baseline levels and reference group. However, the erythrocyte malondialdehyde, conjugated dienes, and lipofuscin levels significantly increased compared to the baseline levels. The glutathione level significantly increased compared with the baseline. Effects of supplementation with α-tocopherol on oxidative damage were not satisfactory. Therefore, there is no reason to administer α-tocopherol to workers chronically exposed to lead as a prophylaxis of lead poisoning.

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.

The Level of Selenium and Oxidative Stress in Workers Chronically Exposed to Lead.

The possible beneficial role of selenium (Se) on the oxidative stress induced by lead (Pb) is still unclear in humans. Therefore, the aim of the present study was to explore the associations among the Se levels, chronic Pb exposure, oxidative stress parameters, and parameters characterizing the function of the antioxidant defense system in men who are occupationally exposed to Pb. Based on the median serum Se concentrations, the 324 study subjects were divided into two subgroups: a subgroup with a low Se level (L-Se) and a subgroup with a high Se level (H-Se). The levels of lead (PbB) and zinc protoporphyrin (ZPP) in the blood and the delta-aminolevulinic acid (ALA) level in the urine served as indices of Pb exposure. The PbB level was significantly lower in the H-Se group compared to that in the L-Se group by 6 %. The levels of 8-hydroxyguanosine and lipofuscin (LPS) and the activity of superoxide dismutase were significantly lower in the H-Se group compared to that in the L-Se group by 17, 19, and 11 %, respectively. However, the glutathione level (GSH) and the activities of glutathione peroxidase (GPx) and catalase were significantly higher by 9, 23, and 3 %. Spearman correlations showed positive associations between the Se level and GPx activity and GSH level. A lower serum Se level in chronically Pb-exposed subjects is associated with higher Pb blood levels and an elevated erythrocyte LPS level, which reflects the intensity of oxidative stress. Besides, in a group of Pb-exposed subjects with lower serum Se level, depleted GSH pool and decreased activity of GPx in erythrocytes were reported. However, the present results are inadequate to recommend Se supplementation for chronic lead exposure at higher doses than would be included in a normal diet except for selenium deficiency.

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.

The Influence of α-Lipoic Acid and Garlic Administration on Biomarkers of Oxidative Stress and Inflammation in Rabbits Exposed to Oxidized Nutrition Oils.

We hypothesized that addition of substances with antioxidant activity could decrease the concentrations of biomarkers of oxidative stress and inflammatory process, thus inhibiting nonalcoholic steatohepatitis development. We investigated the influence of α-lipoic acid (ALA) and garlic administration on the development of adverse changes in rabbit liver and serum under oxidative stress conditions induced with HFD from oxidized oils. We determined 8-hydroxy-2'-deoxyguanosine (8 OHdG) and malondialdehyde (MDA) in liver homogenates, total oxidant status (TOS), lipid peroxides (LOO) and tumor necrosis factor alpha (TNFα) in blood serum, and TNFα and IL-1α genes expression in liver. The results indicate that the intake of dietary ALA and garlic was significantly associated with decreases of 8 OHdG and MDA levels in rabbits' liver tissue as well as TOS and LOO levels in rabbits' serum. Similarly, TNFα and IL-1α gene expressions were suppressed due to ALA and garlic supplementation. The histopathological analysis confirmed that HFD results in liver disorder leading to steatosis. This adverse effect of HFD was ameliorated by the supplementation of ALA and garlic. The obtained results indicate a beneficial effect of ALA and garlic administration by reducing the oxidative stress intensity and the levels of some proinflammatory cytokines in rabbits fed HFD.

Perinatal manganese exposure and hydroxyl radical formation in rat brain.

The present study was designed to investigate the role of pre- and postnatal manganese (Mn) exposure on hydroxyl radical (HO(•)) formation in the brains of dopamine (DA) partially denervated rats (Parkinsonian rats). Wistar rats were given tap water containing 10,000 ppm manganese chloride during the duration of pregnancy and until the time of weaning. Control rat dams consumed tap water without added Mn. Three days after birth, rats of both groups were treated with 6-hydroxydopamine at one of three doses (15, 30, or 67 µg, intraventricular on each side), or saline vehicle. We found that Mn content in the brain, kidney, liver, and bone was significantly elevated in dams exposed to Mn during pregnancy. In neonates, the major organs that accumulated Mn were the femoral bone and liver. However, Mn was not elevated in tissues in adulthood. To determine the possible effect on generation of the reactive species, HO(•) in Mn-induced neurotoxicity, we analyzed the contents of 2.3- and 2.5-dihydroxybenzoic acid (spin trap products of salicylate; HO(•) being an index of in vivo HO(•) generation), as well as antioxidant enzyme activities of superoxide dismutase (SOD) isoenzymes and glutathione S-transferase (GST). 6-OHDA-depletion of DA produced enhanced HO(•) formation in the brain tissue of newborn and adulthood rats that had been exposed to Mn, and the latter effect did not depend on the extent of DA denervation. Additionally, the extraneuronal, microdialysate, content of HO(•) in neostriatum was likewise elevated in 6-OHDA-lesioned rats. Interestingly, there was no difference in extraneuronal HO(•) formation in the neostriatum of Mn-exposed versus control rats. In summary, findings in this study indicate that Mn crosses the placenta but in contrast to other heavy metals, Mn is not deposited long term in tissues. Also, damage to the dopaminergic system acts as a "trigger mechanism," initiating a cascade of adverse events leading to a protracted increase in HO(•) generation, and the effects of Mn and 6-OHDA are compounded. Moreover, HO(•) generation parallels the suppression of SOD isoenzymes and GST in the brains of rats lesioned with 6-OHDA and/or intoxicated with Mn-the most prominent impairments being in frontal cortex, striatum, and brain stem. In conclusion, ontogenetic Mn exposure, resulting in reactive oxygen species, HO(•) formation, represents a risk factor for dopaminergic neurotoxicity and development of neurodegenerative disorders.

The influence of beta-carotene on homocysteine level and oxidative stress in lead-exposed workers.

BACKGROUND: Oxidative stress is involved in lead toxicity. This suggests that some antioxidants may play a role in the treatment of lead poisoning. In the light of this, the aim of the study was to determine whether beta-carotene administration reduces oxidative stress and homocysteine level in workers chronically exposed to lead. MATERIAL AND METHODS: The exposed population included healthy male workers exposed to lead who were randomly divided into 2 groups (mean blood lead level ca. 44 microg/dl). Workers in the 1st group (N = 49, reference group) had no antioxidants, drugs, vitamins or dietary supplements administered, while workers in the 2nd group (N = 33) had beta-carotene administered in a dose of 10 mg per day for 12 weeks. Biochemical analysis included markers of lead-exposure and the level of malondialdehyde (MDA), an oxidative stress biomarker. We also measured the level of homocysteine (Hcy) and thiol groups as well as the activity of superoxide dismutase (SOD) and its isoenzyme EC-SOD in serum. RESULTS: After supplementation, the level of MDA significantly decreased, compared to baseline, by 16%, and to the reference group. When compared to the reference group, Hcy level was also significantly decreased. However, the level of thiol groups was significantly higher after supplementation with beta-carotene compared to the reference group. Analogically, the activity of SOD and EC-SOD was significantly higher compared to the baseline and to the reference group. CONCLUSIONS: Despite some controversies over antioxidant properties of beta-carotene, our results indicate that its antioxidant action could provide some beneficial effects in lead poisoning independent of chelation.

Beta-carotene reduces oxidative stress, improves glutathione metabolism and modifies antioxidant defense systems in lead-exposed workers.

The aim of this study was to determine whether beta-carotene administration reduces oxidative stress and influences antioxidant, mainly glutathione-related, defense systems in workers chronically exposed to lead. The population consisted of two randomly divided groups of healthy male volunteers exposed to lead. Workers in the first group (reference group) were not administered any antioxidants, while workers in the second group (CAR group) were treated orally with 10mg of beta-carotene once a day for 12weeks. Biochemical analysis included measuring markers of lead-exposure and oxidative stress in addition to the levels and activities of selected antioxidants. After treatment, levels of malondialdehyde, lipid hydroperoxides and lipofuscin significantly decreased compared with the reference group. However, the level of glutathione significantly increased compared with the baseline. Treatment with beta-carotene also resulted in significantly decreased glutathione peroxidase activity compared with the reference group, while the activities of other glutathione-related enzymes and of superoxide dismutase were not significantly changed. However, the activities of glucose-6-phosphate dehydrogenase and catalase, as well as the level of alpha-tocopherol, were significantly higher after treatment compared with the baseline. Despite controversy over the antioxidant properties of beta-carotene in vivo, our findings showed reduced oxidative stress after beta-carotene supplementation in chronic lead poisoning.

Assessment of knee function and biochemical parameters of articular fluid and peripheral blood in gonarthrosis patients following intra-articular administration of hyaluronic acid.

BACKGROUND: The development of gonarthrosis (GA) involves inflammatory processes; the role of reactive oxygen species (ROS) is being increasingly mentioned. The body is protected from oxidative damage by the antioxidative barrier with fundamental role being played by antioxidative enzymes, such as superoxide dismutase (SOD), catalase (CAT) and enzymes involved in glutathione transformations, particularly glutathione peroxidase (GPx). The methods of treatment of cartilage depend on the disease advancement, patient's reactions to pain, disease-related impairment in daily activities, as well as the age and overall health of the patient. Viscosupplementation involving intra-articular injection of agents that increase the viscosity of the articular fluid is aimed at reducing the friction between articular surfaces and thus at reducing pain and excessive wear of the remaining articular cartilage. The objective of the study was to examine whether intra-articular administration of a hyaluronic acid agent has any effect on the function of the knee and on the selected biochemical parameters of the articular fluid and blood in gonarthrosis, as well as to demonstrate of correlation or no correlation between the effects of viscosupplementation and administration of hyaluronic acid into a knee containing articular fluid or a "dry" knee. MATERIAL AND METHODS: The study group consisted of 22 gonarthrosis patients who received hyaluronic acid into the knee containing the articular fluid (group PS) as per the study protocol and 27 gonarthrosis patients who received hyaluronic acid into the "dry" knee (group PPI). The study lasted about 40 weeks and involved 10 visits at the study site. Hyaluronic acid was administered intra-articularly upon the first three visits held in one-week intervals, as well as on visit 4 (12 weeks after visit 3). The study knee was assessed clinically at all visits using the osteoarthritis WOMAC scale, visual assessment scale (0-10) for the assessment of pain intensity and HHS questionnaire for clinical assessment of the knee function. Blood for study-related analyses was collected at study start and 12 weeks after administration of the third dose of hyaluronic acid. The activity of superoxide dismutase (SOD) within the articular fluid and plasma and plasma levels of MDA were determined. Results Worse WOMAC-scale quality of life was observed in patients with osteoarthrosis and "dry" knee, mostly due to higher joint stiffness. Following viscosupplementation treatment, improvement in all tested WOMAC scores was observed in both groups, and no significant differences between groups was observed. The SOD activity and the MDA levels in plasma did not differ between the study groups, both before the study and after viscosupplementation. No statistically significant changes were observed in the biochemical parameters following viscosupplementation in both groups other than for reduced articular fluid MDA levels in the PS group. CONCLUSIONS: Viscosupplementation with hyaluronic acid administration is an effective method of conservative treatment in patients with gonarthrosis. Its beneficial effect consists mostly of pain reduction and knee function improvement both in patients with articular fluid present within the knee joints as in patients with "dry" knee joints.

The administration of N-acetylcysteine reduces oxidative stress and regulates glutathione metabolism in the blood cells of workers exposed to lead.

CONTEXT AND OBJECTIVE: The aim of the study was to investigate whether treatment with N-acetylcysteine (NAC) is able to restore erythrocyte glutathione (GSH) content in workers exposed to lead. Additionally, we measured the leukocyte and erythrocyte activities of GSH-related enzymes, such as glutathione reductase (GR), glutathione-S-transferase (GST), and glucose-6-phosphate dehydrogenase (G6PD), and estimated the influence of NAC administration on oxidative stress intensity, which was measured as the lipofuscin (LPS) level in erythrocytes. METHODS: The exposed population consisted of 171 healthy males randomly divided into four groups. Workers in the first group (n = 49) were not administered any antioxidants, drugs, vitamins, or dietary supplements, while workers in the remaining groups were treated with NAC at three doses for 12 weeks (1 × 200 mg per day, 2 × 200 mg per day, and 2 × 400 mg per day). All workers continued to work during the study. The blood of all examined workers was drawn two times: at the beginning of the study and after 12 weeks of treatment. RESULTS AND CONCLUSION: Blood lead levels decreased significantly in all groups receiving NAC compared to those in baseline. Erythrocyte GSH concentrations were significantly elevated in workers receiving 400 and 800 mg of NAC compared to those in baseline by 5% and 6%, respectively. Erythrocyte G6PD activity was significantly elevated in workers receiving 200, 400, and 800 mg of NAC compared to those in baseline by 24%, 14%, and 14%, respectively. By contrast, there were no significant differences in leukocyte G6PD or leukocyte and erythrocyte glutathione reductase (GR) activities before and after treatment. Leukocyte GST activities decreased significantly after treatment in workers receiving 200 mg of NAC by 34%, while LPS levels decreased significantly in workers receiving 200, 400, and 800 mg of NAC compared to those in baseline by 5%, 15%, and 13%, respectively. In conclusion, NAC decreases oxidative stress in workers exposed to lead via stimulating GSH synthesis.

The effect of occupational lead exposure on blood levels of zinc, iron, copper, selenium and related proteins.

The study objective was to evaluate the effect of occupational lead exposure on blood concentrations of zinc, iron, copper, selenium and proteins related to them, such as transferrin, caeruloplasmin and haptoglobin. The examined group consisted of 192 healthy male employees of zinc-lead works. By the degree of lead exposure, the exposed group was subdivided into three subgroups. The control group was composed of 73 healthy male administrative workers. The markers of lead exposure (blood levels of lead and zinc protoporphyrin) were significantly elevated in the exposed group compared with the control group. Additionally, concentrations of copper and caeruloplasmin were raised. The significant increase in haptoglobin level was observed only in the low exposure group. Selenium levels were significantly decreased, whereas iron, zinc and transferrin levels were unchanged in the exposed group compared with the control group. There were positive correlations between the lead toxicity parameters and the copper and caeruloplasmin levels. In conclusion, the effect of occupational exposure to lead on the metabolism of trace metals appears to be limited. However, significant associations between lead exposure and levels of copper and selenium were shown. Changed levels of positive acute-phase proteins, such as caeruloplasmin and haptoglobin, were also observed.

The influence of methionine, selenomethionine, and vitamin E on liver metabolic pathways and steatosis in high-cholesterol fed rabbits.

Significant disorders of liver metabolic pathways enzymes after high-cholesterol diet could give information on liver steatosis development. This process could probably also be inhibited by some compounds, as examined in rabbits. Forty-two male rabbits were served a high-cholesterol diet (2 g%) (0.67 g/kg b.m./24 h) with addition of d,l-methionine (70 mg/kg b.m./24 h) or seleno-d,l-methionine (12.5 microg/kg b.m./24 h) or alpha-tocopherol (10 mg/kg b.m./24 h) for 3 months to compare the protection effect of used compounds on liver metabolism and steatosis. At the beginning and every month, blood was taken. After the experiment was completed, livers were dissected for histological examinations. The concentration of total cholesterol (t-CH), triacylglycerol (TG), and the activities of aldolase (ALD), sorbitol dehydrogenase (SDH), glutamate dehydrogenase (GLDH), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were determined. Plasma t-CH and TG concentrations were significantly higher in all experimental groups vs control group. Blood serum AST and ALT activities did not undergo change but there were observed not significant increase in the CH group vs control group. Activities of SDH, GLDH, and LDH increased in blood serum and decreased in the liver in all experimental groups. Activities of LDH and SDH increased in the liver in the CH+Met group vs CH group. ALD activity decreased in the liver only in the CH and CH+Se groups. This data support a lipotoxic model of cholesterol-mediated hepatic steatosis. Prolonged administration of high-cholesterol diet not only disturbs the structure of cell membranes, which is expressed by decreased activity of enzymes in the liver and the migration of those enzymes to plasma but as well leads to steatosis of the liver, which has been confirmed by histological examinations. The applied compounds appear to have a varying influence upon the activity of enzymes determined in serum and liver. Obtained results showed a beneficial influence of methionine and vitamin E supplementation on liver steatosis development.

Effect of garlic supplementation on erythrocytes antioxidant parameters, lipid peroxidation, and atherosclerotic plaque formation process in oxidized oil-fed rabbits.

Effect of garlic supplementation on blood antioxidant status, lipid peroxidation, and coronary plaque formation process was investigated in oxidized oil-fed rabbits. Eighteen adult male mixed European rabbits were given a balanced diet (21 g% protein, 34 g% fat, 45 g% carbohydrate), which contained isocaloristic addition of nonoxidized or oxidized rapeseed oil in the presence and absence of garlic. The experiment lasted 24 weeks. At the beginning and every 6 weeks, rabbits were weighed, and blood was taken. To evaluate the antioxidant status of the rabbits, erythrocytes malondialdehyde (MDA) concentration, total superoxide dismutase (t-SOD), and glutathione peroxidase (GPX) activations were determined. After the experiment was completed, aortas were dissected for histological examinations. Changes in the contents of the above parameters and histological examinations showed that oxidized rapeseed, oil administered to rabbits, caused the development of atherosclerotic changes and disturbed antioxidant status. The addition of garlic in such diets inhibited atherosclerotic changes in the aorta wall, and it is related to the homeostatic activity of antioxidative enzymes and lipid peroxidation.

Oxidant and anti-oxidant systems of synovial fluid from patients with knee post-traumatic arthritis.

It has been suggested that patients with knee post-traumatic arthritis (PA), associated or not to haemarthrosis (HA), display altered oxidant and anti-oxidant systems in their synovial fluid. This study aimed to establish whether this is really the case. Synovial fluid samples were obtained by transdermal arthrocentesis from 69 patients with PA (36 of them had HA) and 22 control subjects. The activities of synovial fluid zinc-copper superoxide dismutase (ZnCuSOD) and manganese superoxide dismutase (MnSOD) isoenzymes, catalase (CAT), glutathione peroxidase (GPX), glutathione reductase (GR) and glutathione-S-transferase (GST) enzymes, and malondialdehyde (MDA) concentration and synovial fluid viscosity were measured in the study groups. Patients with PA had significantly increased activities of all antioxidant enzymes, except CAT, and MDA concentration than did the controls. However, synovial fluid viscosity was found to be decreased in the study group, mainly in the HA subgroup. Results suggest that excessive free radicals production may exist in synovial fluid of PA patients and may contribute to knee joint destruction.