The Relationship of Methylated Arginines with Urine Cadmium Levels.

BACKGROUND: In this study, we aimed to show that methylated arginines are the predictors of non-clinical atherosclerotic cardiovascular complications in metal workers exposed to Cd. METHODS: The 80 Cd-exposed metal workers and 80 non-exposed workers (control) included in the study were available for measuring arginine, ADMA, SDMA, and L-NMMA levels. RESULTS: The average urine Cd levels (CdU) found were 1.03 ± 0.8 µg/g creatinine (0.84 ± 0.65 µg/L) ranging from 0.01 to 3.00 µg/g creatinine in the control group and 5.41 ± 5.2 µg/g creatinine (4.29 ± 3.81 µg/L) ranged from 0.11 to 27.2 µg/g creatinine in metal workers. On the other hand, the median ratios of the different groups (exposed and control) were found to be 449.35 and 483.88 for arginine/ADMA and 1.28 and 1.33 SDMA/ADMA, respectively. CONCLUSIONS: The present study was undertaken to investigate the relationship between cadmium exposure and methylated arginines such as ADMA/SDMA/L-NMMA parameters which is important for the early detection atherosclerotic cardiovascular diseases.

Assessment of potential cardiovascular risk in trichloroethylene exposure by serum methylated arginine levels.

Trichloroethylene (TCE) is a widely used solvent in industrial applications and has toxic effects on various systems. Methylated arginine amino acids (eg asymmetric dimethyl arginine (ADMA), symmetric dimethyl arginine (SDMA)) cause the development of cardiovascular disease by inhibiting NO synthesis, which is considered to be heart-protector. The aim of this study is to determine the risk of cardiovascular diseases in TCE exposure by methylated arginine biomarkers. About 98 controls and 100 TCE-exposed male subjects were included in the study. Trichloroacetic acid (urinary metabolite of TCE), arginine, homoarginine, citrulline ADMA, SDMA, and N-monomethyl L-arginine (L-NMMA) levels were found significantly higher than control group (p < 0.001). The strongest correlation was found between ADMA and Trichloroacetic acid (TCA) level (r = 0.453, p < 0.01). Long-term TCE exposure, may be an important risk factor for cardiovascular diseases by increasing methylated arginine levels.

Oxidative stress status of Turkish welders.

Welding, a fabrication process that joins metals or thermoplastics by causing coalescence, is indispensable in modern society and ubiquitous in industry. Welding generates fumes that contain several metals and gases that comprise fine and ultrafine particles with the potential for adverse effects. Although health risks of welders have been evaluated in different populations, occupational exposure to welding fumes is still considered to be an important health problem, especially in developing countries. The aim of this study was to investigate the effects of welding fume exposure on important oxidative stress parameters such as superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), total glutathione (GSH), glutathione peroxidase (GPx), malondialdehyde (MDA), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in Turkish welders (n = 48). The influence of confounding factors such as age, smoking habits, alcohol consumption, and duration of exposure on the studied parameters was also analyzed. In our study, significant decreases in the levels of GSH and activities of CAT, SOD, and GPx and significant increases of MDA, 8-OHdG levels and GR activity were found in the workers compared to the controls. There was a negative correlation between GSH levels and alcohol usage. Also, older workers (≥35 years) had significantly higher GR levels than younger workers. But smoking and alcohol usage, duration of exposure, and utilization of protective measures had no significant effect on the studied parameters in the workers. These results indicate that occupational exposure to welding fumes appears to induce oxidative stress and oxidative DNA damage.

Changing levels of selenium and zinc in cadmium-exposed workers: probable association with the intensity of inflammation.

Inflammation is a response mediated by multiple cytokines, such as IL-6, IL-10 and TNF-α. Cadmium (Cd) has been involved in the etiopathogenesis of many diseases via inflammation. Selenium (Se) and zinc (Zn) play a pivotal role in maintaining many physiological functions of cells as well as inhibiting Cd-induced cytotoxicity. This study investigated the anti-inflammatory effects of Se and Zn in cadmium-exposed workers by measuring the levels of IL-6, IL-10 and TNF-α cytokines in 68 control and 91 Cd-exposed subjects. Blood samples were obtained from each participant for immunological, toxicological and routine analysis. All samples were digested by microwave oven and analysed by inductively coupled plasma mass spectrometry (ICP-MS). IL-6, IL-10 and TNF-α cytokine levels were found to be statistically different (p < 0.001) between the control and Cd-exposed groups (23.50 ± 7.70 pg/mL vs. 69.05 ± 19.06 pg/mL; 28.61 ± 9.83 pg/mL vs. 51.79 ± 11.77 pg/mL; 3.44 ± 1.14 pg/mL vs. 5.79 ± 1.04 pg/mL, respectively). High positive correlations were found between Cd levels of participants and IL-6, IL-10, TNF-α and CRP levels (r = 0.568, r = 0.615, r = 0.614 and r = 0.296, respectively, p < 0.01). In terms of the regression analysis results, there were significant effects of Cd on IL-6, IL-10 and TNF-α levels (p < 0.05). The Cd, Zn and Se levels between control and exposed group were significantly different [0.26 ± 0.15 µg/L vs. 3.36 ± 1.80 µg/L; 143.91 ± 71.13 µg/dL vs. 121.09 ± 59.88 µg/dL; 92.98 ± 17.03 µg/L vs. 82.72 ± 34.46 µg/L (p < 0.001, p < 0.03, p < 0.015), respectively]. In conclusion, increasing levels of Se and Zn decreases the intensity of inflammation as measured by IL-6, IL-10 and TNF-α levels.

Arsenic-induced inflammation in workers.

Occupational and environmental exposures to metal and metalloids can result in neurotoxicity and immunotoxicity. Selenium (Se) is essential for the proper functioning of neutrophils, macrophages, natural killer (NK) cells, T-lymphocytes and other immune mechanisms, while zinc (Zn) is a trace element essential for basic cell activities, including cell growth and differentiation. Arsenic (As) may lead to different types of immunosuppressive effects. This study consisted of 62 male workers, who had been exposed to arsenic for different durations and 73 non-exposed male workers (control group) with no history of occupational toxic metal exposure. Whole blood and serum samples were taken from each participant for immunological, toxicological and routine analysis during their annual periodical examination. Arsenic, selenium and zinc levels were determined by the ICP-MS and cytokines, IL-6, IL-10, TNF-α, sE-selectin and VCAM-1, were measured by ELISA. There were statistically significant differences (p < 0.001) between control and As-exposed group in As (1.37 ± 0.42 vs. 4.27 ± 1.54 µg/L) and Se levels (106.37 ± 48.04 vs. 74.70 ± 30.45 µg/L). The changing levels of As, Zn and Se seems to affect the severity of inflammatory reactions based on IL-6, IL-10 and TNF-α levels (r = 0.755, r = 0.679 and r = 0.617, respectively, for all p < 0.01). Selenium was found to have a suppressive effect on cytokines, as evidenced by Pearson correlations and regression analysis. These findings support the need to closely monitor Se levels in individuals exposed to arsenic and benefits for Se supplementation in the case of arsenic exposure, occupationally or environmentally.

Assessment of Endothelial Dysfunction with Methylated Arginines and L-arginine in Cadmium-Exposed People: a Pilot Study.

BACKGROUND: Workers can be exposed to cadmium (Cd) in various industries. On the other hand, another potential source for Cd exposure is the food chain and smoking. Environmental pollution to Cd plays an important role in the development of atherosclerosis. Asymmetric dimethyl arginine (ADMA) levels promote the development of endothelial dysfunction and atherosclerosis-related diseases such as hypertension, acute coronary syndrome, congestive heart failure, and peripheral vascular diseases. The aim of this study is to evaluate the cardiovascular risks of non-symptomatic cadmium-exposed workers and to promote the value of methylated arginines in screening of toxic exposures. METHODS: A total 176 participants were included in the study which has been separated as control group (n = 79) and Cd-exposed group (n = 94). Inductively Coupled Plasma Mass Spectrometry (ICP-MS) was used for toxicological analysis of Cd levels. Also, liquid Chromatography-Mass Spectrometry (LC-MS/MS) was used for levels of methylated arginines such as ADMA, symmetric dimethylarginine (SDMA), NG-monomethyl-L-arginine (L-NM-MA), homoarginine, and citrulline. RESULTS: Statistically significant differences were observed for control and Cd-exposed groups, respectively as follows: Cd levels (0.25 ± 0.13 µg/L and 1.33 ± 0.61 µg/L), ADMA (0.16 ± 0.04 µmol/L and 0.22 ± 0.11 µmol/L), SDMA (0.21 ± 0.06 µmol/L and 0.27 ± 0.07 µmol/L), L-NMMA(0.02 ± 0.01 µmol/L and 0.03 ± 0.01µmol/L), and arginine/ADMA levels (695.82 ± 620.63 and 478.30 ± 432.61). CONCLUSIONS: Our results suggest that workers chronically exposed to Cd showed imbalances in endothelial parameters.

Serum endocan level and diastolic functions in the case of lead exposure

Background/aim: Lead can cause morphological and functional changes in heart, and inflammation and endothelial dysfunction in vasculature. Endocan, as a novel indicator of endothelial dysfunction, has been used for cardiovascular diseases. This study investigated the relationship between lead exposure, endocan levels, and diastolic functions. Materials and methods: A total of 51 lead-exposed workers without a known cardiovascular disease or risk factors and 54 healthy controls were enrolled. All participants underwent transthoracic echocardiography. Blood lead and serum endocan levels were analyzed. Results: Baseline demographic and clinical characteristics were found to be similar between groups. Median blood lead (32 vs 1.5 µg/dL, P < 0.001) and serum endocan levels (67 vs 57.1 pg/mL, P = 0.02) were significantly higher in the lead-exposed group. Serum endocan level showed a positive correlation with blood lead levels (r = 0.404, P = 0.003) in lead-exposed workers. Serum endocan level was an independent risk factor for increased E/E' ratio (ß = 0.704, P = 0.002) and left atrial volume index (ß = 1.158, P = 0.011) and higher level of lead in blood was an independent risk factor for increased E wave (ß = 8.004, P = 0.022) in lead-exposed workers. Conclusion: Worsened diastolic functions may be seen in the course of lead exposure. Due to sharing a similar mechanism, a higher serum level of endocan may be a valuable laboratory clue for impaired diastolic function in this population.

Assessment of DNA damage in ceramic workers.

It is known that ceramic workers are potentially exposed to complex mixture of chemicals such as silica, inorganic lead, lime, beryllium and aluminum that can be associated with an increased risk of several diseases. All operations in the ceramic industries such as mixing, moulding, casting, shaking out and finishing jobs, have been associated with the higher exposure levels and in most of the silica-related industries, average overall exposure exceeded permissible exposure levels for respirable crystalline silica. The aim of this study was to evaluate the possible genotoxic damage in ceramic workers exposed to complex mixture of chemicals mainly crystalline silica. For this purpose, the blood and buccal epithelial cell samples were taken from the ceramic workers (n = 99) and their controls (n = 81). The genotoxicity was assessed by the alkaline comet assay in isolated lymphocytes and whole blood. Micronucleus (MN), binucleated (BN), pyknotic (PYC), condensed chromatin (CC), karyolytic (KYL), karyorrhectic (KHC) and nuclear bud (NBUD) frequencies in buccal epithelial cells and plasma 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) levels were also evaluated. In the study, 38 workers were diagnosed with silicosis, 9 workers were suspected to have silicosis, whereas 52 workers were found to be healthy. DNA damage in blood and lymphocytes; MN, CC + KHC, PYC frequencies in buccal epithelial cells and 8-oxodG levels in plasma were increased in workers compared to their controls. These results showed that occupational chemical mixture exposure in ceramic industry may cause genotoxic damage that can lead to important health problems in the workers.

A new potential biomarker in early diagnosis of firefighter lung function impairment: dynamic thiol/disulphide homeostasis.

OBJECTIVES: The aim of this study was to investigate the associations between urinary arsenic, oxidative stress, assessed by thiol/disulphide homeostasis, and lung diseases in firefighters. METHODS: The study conducted among the municipality-based male firefighters (n = 100) who were admitted to occupational diseases clinic for periodic medical examination. The control group consisted of non-exposed male office workers (n = 50). Urinary arsenic levels, thiol/disulphide homeostasis parameters of participants were determined. Also, lung diseases were assessed by chest X-ray and pulmonary function tests. RESULTS: The mean age and work year did not differ in the study and control group. The median urinary arsenic concentration of firefighters was significantly higher than in the control group: 15.65 (2.5-246) µg/L and 3 (0.10-6) µg/L, respectively (p < 0.001). The parameters of pulmonary function tests (PFT) FVC (%), FEV1 (%), FEV1/FVC ratio and FEF 25-75 (%) were all significantly lower in firefighters compared to controls. A significant increase in mean serum disulphide concentration (17.10 ± 8.31 µmol/L vs. 7.48 ± 5.91) (Fig. 1) and disulphide/native thiol % ratio: 3.63 (0.53-11.43) vs. 1.51 (0.03-7.65) (p < 0.001) were found between exposed group and controls. The Spearman's correlation analysis revealed a positive correlation between urinary arsenic and disulphide (r = 0.422, p < 0.001), disulphide/native thiol % ratio (r = 0.409, p < 0.001). Nevertheless, urinary arsenic correlated negatively with all PFT parameters including FVC (%), FEV1 (%), FEV1/FVC and FEF 25-75 (%) (p < 0.001). CONCLUSION: We showed the arsenic-induced oxidative stress in firefighters with impairments of several lung functions determined by thiol/disulphide homeostasis using a novel method.

Effects of Occupational Silica Exposure on OXIDATIVE Stress and Immune System Parameters in Ceramic Workers in TURKEY.

Silica is the second most common element after oxygen, and therefore, exposures to crystalline silica dust occur in a large variety of occupations such as metal foundries, constructions, and ceramic, quarry, and pottery industries. Since crystalline silica exposure has been linked with silicosis, lung cancer, and other pulmonary diseases, adverse effect attributed to this element has be a cause for concern worldwide. Silica dust exposure in workers is still considered to be important health problem especially in developing countries. The aim of the study was to investigate the effects of occupational silica exposure on oxidative stress parameters including the activities of superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx), and levels of total glutathione (GSH) and thiobarbituric acid reactive substance (TBARS) as well as immune system parameters such as interleukin (IL)-1α, IL-1ß, IL-2, IL-4, IL-6, and IL-10 and tumor necrosis factor (TNF)-α in Turkish ceramic workers. In this study, nearly 50% of Turkish ceramic workers were diagnosed with silicosis. Eighty-four percent of these silicotic workers were found to present with profusion category 1 silicosis, whereas controls (n = 81) all displayed normal chest radiographs. Data demonstrated a significant decrease in levels of GSH and activities of CAT, SOD, and GPx, but a significant increase in MDA levels and activity of GR in all workers. Further, workers possessed significantly higher levels of IL-1α, IL-1ß, IL-2, IL-4, IL-6, IL-10, and TNF-α. These observations suggest that ceramic workers may have impaired antioxidant/oxidant status and activated immune system indicative of inflammatory responses.

The relationship between impaired lung functions and cytokine levels in formaldehyde exposure.

Exposure to formaldehyde (FA) causes detrimental effects on respiratory system. Inflammation is one of the mechanisms responsible for these effects. Our aim is to demonstrate the possible effect of formaldehyde on inflammation biomarkers and pulmonary function tests. One hundred ninety-eight male workers in a fiber production factory are included. Eighty two of them were not exposed to FA. Thirty nine workers were exposed to FA for 4 h or more in a work shift and 77 workers were exposed less than 4 h. Statistically significant differences were found for FA, TNF-α, and IL-6 levels and pulmonary function test parameters (FEV1 and FVC) between no exposure and exposure groups. The results revealed a correlation between decrement in pulmonary function tests and an increase in cytokine levels concordant with the duration of FA exposure. The results may emphasize that FA exposure shows its effect on pulmonary system via inflammatory pathways.

The effects of occupational lead exposure on selected inflammatory biomarkers.

In exposure to toxic metals such as lead, determining lead and cytokine levels (IL-6, IL-10, and TNF-α) is essential for early detection of diseases. The aim of this study was to develop an model for early detection of inflammation and onset of atherosclerosis in the absence of clinical findings in young workers, which could help physicians take timely an action and start treatment. This study included 49 metal workers exposed to lead occupationally and 50 unexposed administrative workers (controls) who underwent immunological analysis for cytokines (IL-6, IL-10, and TNF-α) and atherosclerosis markers (h-FABP and VCAM-1), toxicological analysis for lead, and routine biochemical analysis (ALT, AST, creatinine) at the Ankara Occupational and Environmental Diseases Hospital in 2017. Lead levels correlated with IL-6, IL-10, and TNF-α (r=0.469, r=0.521 and r=0.279, respectively, p<0.01) but did not significantly affect h-FABP and VCAM-1 levels.

Assessment of DNA damage in welders using comet and micronucleus assays.

Welding technology is widely used in pressurized containers, thermal power plants, refineries, chemical facilities and steel structures. Welders are exposed to a number of hazardous compounds such as ultraviolet (UV) radiation, electromagnetic fields, toxic metals and polycyclic aromatic hydrocarbons (PAHs). In the present study, 48 welders and an equal number of control subjects were evaluated for DNA damage in the whole blood and isolated lymphocytes using the comet assay. The genotoxic damage in buccal epithelial cells of subjects was determined by micronucleus (MN) assay. Metal(loids) such as Cr, Mn, Ni, Cu, As, Cd and Pb levels in blood samples were evaluated by using Inductively Coupled Plasma-Mass Spectrometer (ICP-MS). Results of this study showed that DNA damage in blood, isolated lymphocytes, and buccal epithelial cells were significantly higher in workers compared to the controls. Also, these workers had remarkably higher blood Cr, Cu, Cd, Ni and Pb levels. These results showed that occupational exposure to welding fumes may cause genotoxic damage that can lead to important health problems in the workers. More extensive epidemiological studies should be performed that enable the assessment of health risk in welding industry.

TNF-α and IL-6 as Biomarkers of Impaired Lung Functions in Dimethylacetamide Exposure.

BACKGROUND: Tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) are well-known biomarkers of systemic inflammation that have been associated with many diseases in the past. In this study, we aimed to determine the relationship between impaired lung functions and the levels of these biomarkers in DMAc exposed people. METHODS: 101 non-exposed control subjects (Group 1) and 109 DMAc-exposed workers from the polyvinyl chloride (PVC) industry were included in the study. In the next step, the exposed group was divided into two groups according to the level of exposure (Group 2 and 3). DMAc, TNF-α, IL-6, creatinine, ALT, AST, GFR and standard spirometry measurements were carried out in all subjects. RESULTS: When compared to the control group, TNF-α and IL-6 levels were significantly high compatible with the increase of DMAc levels, in the exposed groups. Urinary DMAc Levels were 0.06 mg/L in the control group. This level is significantly low when compared to exposed and severely exposed group (2.43 mg/L and 3.17 mg/L). TNF-α levels were 56.86 pg/mL, 145.52 pg/mL and 230.52 pg/mL in control, exposed and severely exposed groups. IL-6 levels were found to be 38.08 pg/mL, 89.19 pg/mL and 116 pg/mL for control, exposed and severely exposed groups, respectively. Similarly, the FEV1/FVC ratio decreased especially in the severely exposed group (p 0.001). CONCLUSIONS: In our study, results have revealed that TNF-and IL-6 levels are promising biomarkers in the early diagnosis of lung function impairment in inhalational DMAc exposure.

Evaluation of Dynamic Disulphide/Thiol Homeostasis in Silica Exposed Workers.

BACKGROUND: Oxidative stress is implicated as one of the main molecular mechanism underlying silicosis. AIMS: In this study, our aim was to asses the redox status in occupationally silica-exposed workers, by evaluating the dynamic thiol-disulphide homeostasis. STUDY DESIGN: Case-control study. METHODS: Thirty-six male workers occupationally exposed to silica particles and 30 healthy volunteers, working as office workers were included to the study. Posteroanterior chest radiographs and pulmonary function tests of both groups were evaluated. Also serum thiol disulphide levels were measured using the spectrophotometric method described by Erel and Neselioglu. RESULTS: Among the 36 workers that underwent pulmonary function tests 6 (17%) had obstructive, 7 (19%) had restrictive, 6 (17%) had obstructive and restrictive signs whereas 17 (47%) had no signs. The mean PFTs results of silica-exposed workers were significantly lower than control subjects. The serum disulphide levels of silica-exposed workers were significantly higher than control subjects (23.84±5.89 µmol/L and 21.18±3.44 µmol/L, respectively p=0.02). CONCLUSION: The serum disulphide levels, a biomarker of oxidative stress, are found to be higher in silica-exposed workers.