Cobalt's role in modulating antioxidant systems and semen quality in males.

The present study investigated associations between environmental exposure to cobalt (Co) and the levels of oxidative stress parameters and the antioxidant defense system in the seminal plasma of fertile males. The study population consisted of 117 healthy, non-smoking, fertile men from the southern region of Poland. The study was carried out in 2021-22. Based on the median cobalt levels in seminal plasma, subjects were divided into two groups: those with low (Co-L) and high (Co-H) cobalt concentrations. Semen parameters assessed according to WHO 2021 recommendations. After the analysis of spermiograms, observed reduction in progressive motility after 1 h was found in the Co-H group. Moreover, superoxide dismutase (SOD), glutathione S-transferase (GST) in the Co-H group had lower activity and GR higher activity. The OSI (Oxidative stress index) were higher in the group with high cobalt concentration in semen. The concentrations of redox balance parameters: TOS, TAC and OSI significantly were higher in the Co-high group as well as GR activity. Environmental exposure to cobalt decreases sperm motility in both normal and abnormal semen. The findings from this study affirm that cobalt can induce oxidative stress and alter oxidative stress markers in semen.

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.

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.

Critical aspects of the physiological interactions between lead and magnesium.

Despite technological progress, exposure to lead is an ongoing problem. There are many mechanisms governing the toxic effects of lead on the human body. One such mechanism involves the interaction of this xenobiotic with bivalent metal ions, including magnesium. Literature data suggest that the competition between these elements for binding sites at the molecular and cellular levels, as well as at the systemic level, may represent an important aspect of lead toxicity in the human body. This is especially clear in the context of oxidative stress, immune response, and gene expression modifications. This review aims to summarize current knowledge regarding these issues.

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.

Blood Magnesium Level and Selected Oxidative Stress Indices in Lead-Exposed Workers.

Occupational exposure to lead is one of the important hazards to human global population. Lead interferes with divalent cations, such as calcium, magnesium, and iron. Magnesium is the fourth most common mineral in the human body and a cofactor in more than 325 enzymes. There are many disorders associated with magnesium deficiency. It has been postulated that hypomagnesemia promotes oxidative stress. Study population included 232 male employees of lead-zinc works and was divided into two sub-groups based on the median of magnesium serum level: low magnesium level (L-Mg) group and high magnesium level (H-Mg) group. Magnesium level was significantly higher in the H-Mg group than in the L-Mg group due to the study design. The level of zinc protoporphyrin was significantly higher in the L-Mg group than in the H-Mg group by 13%, while the blood lead levels were similar in the examined groups. The serum level of MDA was significantly higher in the L-Mg group than in the H-Mg group by 12%, while the serum levels of thiol groups, TAC, and bilirubin were significantly lower in that group by 6%, 3%, and 27%, respectively. Similarly, the erythrocyte SOD activity was lower in the L-Mg group than in the H-Mg group by 5%. Low serum magnesium levels contribute to lead-induced oxidative stress, result in unfavorable modification of antioxidant system function, and promote lead-induced impairment of heme synthesis. Obtained results indicate that prevention of hypomagnesemia should be regarded as an important step in ensuring adequate prophylaxis of chronic lead poisoning.

Potential Antioxidant Activity of Calcium and Selected Oxidative Stress Markers in Lead- and Cadmium-Exposed Workers.

Occupational lead (Pb) and cadmium (Cd) exposure occurs during processing and casting of nonferrous metals such as zinc. In contrast to Pb and Cd, Ca is essential for living organisms due to its important role in a multitude of functions, from cell signaling to bone growth. Pb and Cd exposure affects calcium metabolism in various ways. The aim of this study was to investigate the blood levels of Pb, Cd, and Ca and the levels of selected oxidative stress biomarkers in workers exposed to Pb and Cd. Population groups included 264 male employees in a lead-zinc smelter. The study population was divided into two subgroups based on the median of Ca serum level (2.42 mmol/l): the low-Ca-level group (L-Ca group) and the high-Ca-level group (H-Ca group). Ca level was significantly higher in the H-Ca group than in the L-Ca group due to the study design (by 26%). The level of zinc protoporphyrin (ZPP) was significantly higher in the L-Ca group than in the H-Ca group by 13%, while the blood lead levels (PbB) were similar in the examined groups. The level of cadmium (CdB) was significantly higher in the L-Ca group than in the H-Ca group by 33%. From oxidative stress markers in serum, only the levels of malondialdehyde (MDA) and ceruloplasmin (CER) were significantly higher in the L-Ca group than in the H-Ca group, by 12% and 4%, respectively. The correlation analysis showed negative correlations between Ca level and the levels of PbB, ZPP, CdB, and MDA. The presented results indicate that Ca level modulates the serum concentration of Cd and has an impact on Pb-induced impairment of heme synthesis. The higher Ca levels may lead to a decrease in the concentration of lipid peroxidation products. Moreover, serum calcium level seems to be able to modify the level of acute-phase proteins. Obtained results suggest that higher Ca level may be useful in reducing Cd level in occupationally exposed workers.

Oxidative Stress is Associated with Reduced Sperm Motility in Normal Semen.

Infertility is among the most serious medical problems worldwide. Male factors contribute to 40%-50% of all infertility cases, and approximately 7% of men worldwide are affected by infertility. Spermatozoa are extremely vulnerable to oxidative insult. Oxidative stress results in axonemal damage and increased midpiece sperm morphological defects, which lead to reduced sperm motility. The aim of the study is to evaluate the association between sperm motility and the levels of selected antioxidants, cytokines, and markers of oxidative damage in the seminal plasma.The study group included 107 healthy males, who were split into two subgroups based on the percentage of motile spermatozoa after 1 hr: low motility (LM, n = 51) and high motility (HM, n = 56).The glucose-6-phosphate dehydrogenase (G6PD) activity was 52% lower in the LM group compared to that in the HM group. The level of malondialdehyde (MDA) was 12% higher in the LM group compared to that in the HM group. Similarly, the median values of interleukin (IL)-1ß, IL-10, IL-12, and tumor necrosis factor alpha (TNF-α) were higher in the LM group than those in the HM group. Results of the present study revealed that the percentage of motile spermatozoa after 1 hr correlated positively with the levels of IL-1ß, IL-10, IL-12, and TNFα.The lower motility of spermatozoa in healthy men is associated with a decreased activity of G6PD and increased levels of cytokines, which may be related to increased oxidative stress in seminal plasma that manifests as an increased level of MDA.

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.

The Role of Oxidative Stress, Selected Metals, and Parameters of the Immune System in Male Fertility.

The aim of the study was to investigate the associations between standard semen parameters and the parameters reflecting oxidative stress intensity, antioxidant defense functions, levels of selected macro and trace elements, and parameters characterizing immune system function. The study group consisted of 103 fertile males. Based on semen volume, sperm concentration, total sperm count, and percentage of motile sperm at 1 hour postcollection, the individuals were divided into two equal groups-those with excellent (EX) semen quality and those with mediocre (ME) semen quality. The remaining measured parameters characterizing motility and the percentage of normal morphology were higher in the EX group than in the ME group; however, the seminal plasma pH did not differ between the examined groups. The phosphate level was 31% lower in the EX group than in the ME group, whereas there was a tendency toward a 25% lower level of Fe in the EX group than in the ME group (p = 0.064). The activities of enzymes involved in antioxidant defense, CuZn-SOD, CAT, and G6PD, were 14%, 63%, and 39%, respectively, higher in the EX group than in the ME group. However, the level of alpha-tocopherol was 32% lower in the EX group than in the ME group. The other measured parameters characterizing antioxidant defense and the parameters of oxidative stress intensity and immune system function were not significantly different. The value of seminal plasma pH is not related to the semen quality of fertile males. Higher fertility potential estimated based on standard semen parameters in fertile males is associated with lower levels of Fe and higher activities of some antioxidant enzymes.

The Associations between Infertility and Antioxidants, Proinflammatory Cytokines, and Chemokines.

The aim of the study was to evaluate the parameters of oxidative stress and antioxidant defense in relation to the levels of proinflammatory cytokines and chemokines in patients diagnosed with oligozoospermia and asthenozoospermia. Based on the basic parameters of the spermogram, the examined group (n = 243) was divided into three groups: oligospermic group (sperm count less than 15 × 106/ml) consisting of 152 men, astenozoospermic group (less than 40% of progressively moving sperm cells) consisting of 142 men, and oligoastenozoospermic group (both criteria met) consisting of 90 men. The control group consisted of 103 males with normal semen profile according to the WHO criteria. Total superoxide dismutase (SOD) activity in seminal plasma and spermatozoa lysate was significantly lower by 12% and 22%, respectively, in males with oligospermia than in the control group. Analogically, Mn-SOD activity in spermatozoa lysate was significantly lower in males with oligospermia, asthenospermia, and oligoasthenospermia by 44%, 32%, and 45%, respectively. By contrast, CuZn-SOD activity in spermatozoa lysate was significantly higher in males with oligospermia by 60%. The activity of glutathione peroxidase (GPx) in seminal plasma was also significantly higher in males with oligospermia and oligoasthenospermia by 56% and 78%, respectively. The level of malondialdehyde (MDA) in seminal plasma was significantly higher in males with asthenospermia than in the control group by 12%. By contrast, the level of MDA in spermatozoa lysate was significantly lower in males with oligospermia, asthenospermia, and oligoasthenospermia by 26%, 20%, and 26%, respectively. The level of interleukin- (IL-) 8 in seminal plasma was significantly higher in males with asthenospermia and oligoasthenospermia by 64% and 67%, respectively. Abnormalities in spermogram, such as oligospermia, asthenospermia, and oligoasthenospermia, may be related to a decreased activity of Mn-SOD in spermatozoa and increased levels of chemokines in seminal plasma.

The effect of subacute lead exposure on selected blood inflammatory biomarkers and angiogenetic factors.

OBJECTIVES: The aim of the study was to examine blood levels of selected pro-inflammatory cytokines, C reactive protein (CRP), and selected factors that influence angiogenesis in workers exposed to lead for a short period of time. METHODS: The study population consisted of 36 male workers (mean age 41 ± 14 years) exposed to lead for 40 days. RESULTS: The mean blood lead level (BLL) was 10.7 ± 7.67 µg/dl at the beginning of the study, and increased to 49.1 ± 14.1 µg/dl at the end of the study period. The levels of macrophage inflammatory protein 1-α (MIP-1α) were significantly higher after the studied exposure to lead compared to the baseline by 71%. Similarly, the values of CRP increased by 35%. Conversely, the values of soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) and fibroblast growth factor-basic (FGF-basic) decreased by 14% and 21%, respectively. After the examined period of lead exposure, analysis of correlations showed positive correlations between vascular endothelial growth factor (VEGF) levels and the levels of interleukin 1ß (IL-1ß) (R = 0.39), interleukin 6 (IL-6) (R = 0.42), and MIP-1α (R = 0.54). Positive correlations were identified between MIP-1α and FGF-basic (R = 0.38), soluble angiopoietin receptor (sTie-2) (R = 0.41), and sVEGFR-1 (R = 0.47). DISCUSSION: Short-term exposure to lead induces the inflammatory response; however, these mechanisms seem to be different from those observed in chronic lead exposure. Subacute exposure to lead may dysregulate angiogenesis via modifications in the levels of angiogenic factors.

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.

Cytokines related to three major types of cell-mediated immunity in short- and long-term exposures to lead compounds.

Many investigators have posited on the significant influence of lead on the immune system function. However, available data on this topic are not conclusive. Therefore, a study was undertaken to examine associations between lead exposure and levels of cytokines related to the T-helper (TH)-1, TH2, and TH17 types of immune response in humans. For these analyses, three population groups were examined: the first consisted of male workers exposed to lead for a short period of time (36-44 days); the second included male workers chronically exposed to lead (13 ± 10 years); and a control group that was composed of male administrative workers with blood lead levels (BLL) < 10 µg/dl. BLL were determined for all study subjects. Thereafter, serum samples were analyzed for the levels of interleukin (IL)-2 (IL-2), IL-4, IL-5, IL-12, IL-13, IL-17A, and interferon (IFN)-γ using a multi-analyte system. The results indicated that the levels of IFNγ IL-2, IL-12 (related to TH1 cells), IL-4, IL-5, IL-13 (related to TH2 cells), and IL-17A (related to TH17 cells) did not change after a short-term exposure to lead (compared to baseline). However, the levels of all of these cytokines were significantly higher in workers chronically exposed to lead than in the controls by 82%, 32%, 81%, 22%, 70%, 42%, and 17% (IFNγ, IL-2, IL-12, IL-4, IL-5, IL-13, IL-17A, respectively). From these studies, we conclude that in humans, a short-term exposure to lead does not affect levels of cytokines related to the TH1-, TH2-, and TH17-mediated immune responses, while chronic exposure modifies their levels. Taken together, these modifications do not evidence an ability of lead to promote specifically one type of immune response in an exposed host.