Effect of occupational co-exposure to lead and cadmium on selected immunomodulatory cytokines

Occupational exposure to heavy metals like lead (Pb) and cadmium (Cd) is associated with the development of several diseases. The objective of this study was to determine the effect of occupational co-exposure to Pb and Cd on the blood levels of selected immune-modulatory cytokines related to T helper (Th), that is, Th1, interleukin-2 (IL-2), Th2, (IL-4 and IL-10), and Th17, (IL-17) cells. The study comprised 207 individuals divided into two groups: exposed ( n = 110) and nonexposed ( n = 97). Blood Pb and Cd were determined using Graphite Furnace Atomic Absorption Spectroscopy, and serum levels of cytokines were measured using enzyme-linked immunosorbent assay (ELISA). The study revealed significantly higher blood Pb and Cd levels in the exposed group. A significant decrease in Th1 cytokine-IL-2 and Th2 cytokine-IL-10 was found, while IL-4 (Th2 cytokine) and IL-17 (Th17) levels were higher in the exposed group. In the mixed exposure analysis, among all the selected cytokines, IL-4 levels were significantly different between individuals having higher levels of both Pb and Cd versus lower levels of Pb and Cd. While IL-2 levels were highest among the low Pb and Cd group, the IL-17 levels were highest among individuals with higher Cd levels. The study demonstrated that co-exposure to low levels of Pb and Cd might have an immune-modulatory effect. The data suggested a metal-induced pro-inflammatory immune response.

Evaluation of blood lead among painters of buildings and cars

Exposure to lead-based paints is a major threat to the health of painters. This study aimed to evaluate the blood concentration of lead (Pb) in painters of buildings and cars. The present study was a cross-sectional study in which a semi-structured questionnaire was used to collect the socio-demographic information. Lead concentration in blood samples was determined using the atomic absorption spectrometry method. A total of 32 male painters were selected based on inclusion criteria. The mean blood lead level (BLL) in the painters was 8.1 ± 4.93 μg/dL. Pb levels in car and building painters were 9.42 ± 5.5 μg/dL and 6.7 ± 1.85 μg/dL, respectively. Pb concentration in none of the blood samples was more than 30 μg/dL. The prevalence of BLL ≥ 5 μg/dL and BLL ≥ 10 μg/dL was 97% and 19%, respectively. According to the findings, the rate of BLL among car painters was higher than building painters. Considering the presence of Pb in all blood samples, it seems necessary to increase the awareness of painters about the adverse effects of lead exposure even in low concentrations. However, the sample size in this study was small and more investigations are required in this regard.

Intraperitoneal exposure of iron oxide nanoparticles causes dose-dependent toxicity in Wistar rats

Nanoparticles of iron oxide, with diameters beteween 1 to 100 nm, have notable implications for human health and well being. In the current study, we have investigated the effects of iron oxide nanoparticles (IONP) exposure on general physiology and health of adult Wistar rats. IONP used in the study had spherical shape and average size in the range of 15–20 nm. A total of eight groups of rats were repeatedly injected with 0 (control), 20, 40, and 80 mg IONP per kg body weight intraperitoneally under two different exposure schemes (sub-acute and sub-chronic). IONP exposure caused significant changes in lungs, liver, and kidney indices in both exposure schemes. Sub-acute exposure did not affect body weight gain in treated rats, but longer duration exposure was responsible for significant reduction in body weight. Mesenteries, visceral fatty tissues, and visceral peritoneal membranes demonstrated apparent accumulations of IONP in a dose and time-dependent manner. Hematological analysis showed that total RBC count, hemoglobin content, hematocrit, mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC) and mean platelet volume (MPV) were not affected by IONP exposure. Total lymphocyte count, however, was elevated in low- and mid-dose treated rats, but not in high-dose group. Serum lactate dehydrogenase (LDH) increased significantly in rats treated with mid and high doses as compared to control. Serum creatinine and blood urea nitrogen levels were also significantly altered in treated rats. Histological study found significant hepatic damage and mild spleen toxicity. Our report suggests that IONP exhibit significant toxicity in rats.

Long non-coding RNA ENST00000414355 as a biomarker of cadmium exposure regulates DNA damage and apoptosis

Human exposure to cadmium (Cd) may induce severe effects in different organs. Recent studies suggest that long non-coding RNAs (lncRNAs) are closely involved in the pathophysiological mechanisms of Cd-related diseases. This study evaluated the use of lncRNA (ENST00000414355) as an expression signature of Cd exposure and assessed its ability to modulate DNA damage and apoptosis by measuring the expression of ATM serine/threonine kinase (ATM) and mitochondrial membrane potential (ΔΨm) in Cd-exposed workers. A total of 139 (74 non-smokers and 65 smokers) participants from a Cd battery manufacturer were included in the study. Venous blood samples were collected to determine the blood Cd level and detect blood ENST00000414355 and its target gene (ATM) using real-time reverse transcription-polymerase chain reaction (qRT-PCR). Mitochondrial membrane potential was used to assess the Cd effect on mitochondrial permeability. Our results indicated a significant positive correlation between blood Cd level and lncRNA-ENST00000414355 and ATM expression and a significant negative correlation between blood Cd level and ΔΨm ( p < 0.0001). Moreover, significant correlations were observed between the expression of lncRNA-ENST00000414355 and ATM expression and ΔΨm ( p < 0.0001). Statistical significance was found in the blood Cd level, lncRNA-ENST00000414355 expression, ATM expression, and ΔΨm ( p < 0.0001) between smokers and non-smokers. This study confirmed the upregulation of the lncRNA-ENST00000414355 expression, DNA damage-checkpoint-related gene (ATM), and decreased ΔΨm in Cd-exposed workers. Thus, lncRNA-ENST00000414355 may serve as a valuable biomarker for the exposure and toxicity of Cd.

Accelerated apoptosis, oxidative stress, and cholinergic inflammation in blood of metalworkers

Metalworkers are exposed to numerous chemicals in their workplace environment, such as solvents, heavy metals, and metalworking fluids, that have a negative impact on their health. Furthermore, there is an increase in the prevalence of chronic diseases among metalworkers; however, the molecular mechanisms involved in this increased predisposition to chronic diseases are unclear. Considering that occupational exposure represents a potential risk for metalworkers, the aim of this study was to measure biomarkers of oxidative stress, inflammation, and cytotoxicity in the peripheral blood of metalworkers from Southern Brazil. The study included 40 metalworkers and 20 individuals who did not perform activities with any recognized exposure to chemical substances, such as those working in administration, commerce, and education, as controls. Cellular and molecular biomarkers as leukocyte viability, intracellular production of reactive species, mitochondrial mass and membrane potential and plasma lipid peroxidation, sulfhydryl groups, total antioxidant capacity, and butyrylcholinesterase activity were evaluated in the blood of metalworkers and controls. Metalworkers were found to have higher rates of apoptosis, increased production of reactive species, and increased mitochondrial potential and mass in leukocytes associated with decreased antioxidant defenses and increased activity of the butyrylcholinesterase enzyme in their plasma. It can be concluded that cytotoxicity, oxidative stress, and inflammation are involved in the multiplicity of health outcomes related to chemical exposure in the metalworking industry.

The effect of maternal exposure to titanium dioxide nanoparticles on the pain response in offspring mice using formalin test

This study was conducted to evaluate the effect of maternal exposure to TiO2 nanoparticles on the pain response in offspring mice. 30 female mice with a mean ± SD weight of 30 ± 5 g were randomly divided into three groups: the control group (group 1) received only the basal diet; the sham group (group 2) received saline plus as a carrier (100 μL/mice) subcutaneously on days 3, 7, 10, and 14 post-mating; and the test group (group 3) received 100 μL/mice TNPs subcutaneously on days 3, 7, 10, and 14 post-mating. Offspring were divided into 6 groups 21 days after birth and underwent formalin test. Blood samples were taken to evaluate possible oxidative changes in total antioxidant capacity (TAC) and malondialdehyde (MDA). Exposure to TNPs significantly ( p < 0.05) decreased pain perception. Except for a significant difference between the sham group and the control group, MDA and TAC were not significantly different among the studied groups. Injection of TNPs to pregnant mice would affect the pain perception in their offspring. This may be attributable to the ability of these particles to pass through the placenta to produce free radicals.

Polymorphisms of the AS3MT gene are associated with arsenic methylation capacity and damage to the P21 gene in arsenic trioxide plant workers

Epidemiological evidence suggests that the metabolic profiles of each individual exposed to arsenic (As) are related to the risk of cancer, coronary heart disease, and diabetes. The arsenite methyltransferase ( AS3MT) gene plays a key role in As metabolism. Several single nucleotide polymorphisms in the AS3MT gene may affect both enzyme activity and gene transcription. AS3MT polymorphisms are associated with the proportions of monomethylarsenic acid (MMA) and dimethylarsenic acid (DMA) in urine as well as the incidence of cancer. P21 protein is a cyclin-dependent kinase inhibitor. Mutations of the P21 gene have been found in cancer patients. In our study, we investigate whether polymorphisms of the AS3MT gene alter As methylation capacity and adversely affect the P21 gene in arsenic trioxide plant workers. The DNA damage was examined by the quantitative polymerase chain reaction. Restriction fragment length polymorphism was used to analyze the genotype of the AS3MT gene. The results showed that DNA damage in P21 gene fragments was greater in those individuals exposed to high levels of As. There was a strong positive correlation between the DNA damage to P21 gene fragments and the percentage of MMA in urine. However, DNA damage in P21 gene fragments was negatively associated with the percentage of DMA in urine (%uDMA), primary methylation index (PMI), and secondary methylation index. We found that subjects with the rs7085104 GG or GA allele were associated with higher %uDMA and PMI and less DNA damage. The subjects with the rs11191454 GG+GA or GA allele were also associated with higher %uDMA and PMI and less DNA damage. Our results suggest that rs1191454 and rs7085104 in the AS3MT gene affect the As-induced DNA damage by altering individual metabolic efficiency.

Manganese exposure causes movement deficit and changes in the protein profile of the external globus pallidus in Sprague Dawley rats

Manganese (Mn) is required for normal brain development and function. Excess Mn may trigger a parkinsonian movement disorder but the underlying mechanisms are incompletely understood. We explored changes in the brain proteomic profile and movement behavior of adult Sprague Dawley (SD) rats systemically treated with or without 1.0 mg/mL MnCl2 for 3 months. Mn treatment significantly increased the concentration of protein-bound Mn in the external globus pallidus (GP), as demonstrated by inductively coupled plasma mass spectrometry. Behavioral study showed that Mn treatment induced movement deficits, especially of skilled movement. Proteome analysis by two-dimensional fluorescence difference gel electrophoresis coupled with mass spectrometry revealed 13 differentially expressed proteins in the GP of Mn-treated versus Mn-untreated SD rats. The differentially expressed proteins were mostly involved in glycolysis, metabolic pathways, and response to hypoxia. Selected pathway class analysis of differentially expressed GP proteins, which included phosphoglycerate mutase 1 (PGAM1), primarily identified enrichment in glycolytic process and innate immune response. In conclusion, perturbation of brain energy production and innate immune response, in which PGAM1 has key roles, may contribute to the movement disorder associated with Mn neurotoxicity.

Blood lead levels, calcium metabolism and bone-turnover among automobile technicians in Sagamu, Nigeria: Implications for elevated risk of susceptibility to bone diseases

Lead is an occupational toxicant and a recognised health threat particularly in developing countries. Hence, this study explored the interaction of blood lead level (BLL), a conventional marker of lead exposure, with indices of calcium metabolism and biomarkers of bone-turnover in 120 adult male automobile technicians (AT) with ≥ 1 year duration in professional practice. The AT as well as the control group, which comprised 120 age, body-size and socio-economically matched male administrative workers, were recruited from Sagamu, South West Nigeria. Levels of blood lead, serum indices of calcium metabolism [total calcium (tCa), ionised calcium (iCa), phosphate, albumin, magnesium (Mg) and 25-Hydroxycholecalceferol (25-OHCC)], biomarkers of bone formation [bone alkaline phosphatase (BALP) and osteocalcin (OC)] and biomarkers of bone resorption [tartarate-resistant acid phosphatase-5b (TACRP-5b) and urinary hydroxyproline (UHYP)] were determined in all participants. The BLL, 25-OHCC, TRACP-5b and UHYP significantly increased while tCa and iCa significantly reduced in AT compared to control. However, no significant difference was observed in phosphate, albumin, Mg, BALP and OC in AT compared to control. Interestingly, BLL demonstrated a significant negative association with tCa and iCa but a significant positive association with 25-OHCC, TRACP-5b and UHYP. However, BLL did not show significant association with phosphate, albumin, Mg, BALP and OC. Increased lead exposure as well as altered calcium metabolism and bone-turnover demonstrated by the automobile technicians may be suggestive of lead-induced accelerated bone demineralisation. These workers may be predisposed to high risk of increased susceptibility to bone diseases if this sub-clinical picture is sustained.

Formaldehyde induces ferritinophagy to damage hippocampal neuronal cells

Formaldehyde (FA) causes neurotoxicity and contributes to the occurrence of neurodegenerative diseases. However, the mechanism of FA-induced neurotoxicity has not been fully elucidated. Ferritinophagy, an autophagy process of ferritin mediated by the nuclear receptor coactivator 4 (NCOA4), is a potential mechanism of neurotoxicity. In this study, we explored whether ferritinophagy is associated with the neurotoxicity of FA. Our results showed that FA (50, 100, 200 μM; 24 h) exposure upregulated ferritinophagy in the mouse hippocampal neuronal HT22 cells, which was evidenced by the upregulated autophagic flux, the increased colocalizations of NCOA4 with ferritin heavy chain (FTH1) and NCOA4 with microtubule-associated protein 1 light chain-3B (LC3B), the augmented expression of NCOA4, and the reduced content of FTH1. We also found that FA (0.1, 1, and 10 μmol, i.c.v., 7d) administration boosted ferritinophagy in the hippocampus of Sprague-Dawley (SD) rats, which was demonstrated by the accumulated autophagosomes, the increased expressions of LC3II/I and NCOA4, and the decreased contents of p62 and FTH1 in the hippocampus. Further, we confirmed that inhibition of ferritinophagy by silencing the expression of NCOA4 decreased FA-induced toxic damage in HT22 cells. These results indicated that FA induces neurotoxicity by promoting ferritinophagy. Our findings suggest a potential mechanism insight into the FA-induced neurotoxicity, which in turn provides a new thought for the treatment of FA-related neurodegenerative diseases.