Low concentrations of lead disturb phenotypical markers of the inflammatory and the anti-inflammatory profile of bone marrow-derived macrophages from BALB/c mice.

Lead (Pb) is a ubiquitous toxic metal that decreases resistance to infections, in which the macrophages have an essential role. Pb adverse effects on nitric oxide (NO-) production and variable effects on inflammatory cytokines in activated macrophages have been reported, but no effects have been reported in anti-inflammatory macrophages. We studied Pb (0.03-6 µg/dL equivalent to 0.014-2.89 µM) effects on the function of bone marrow-derived macrophages (BMDM) induced to either inflammatory or anti-inflammatory phenotypes, with LPS + IFNγ or IL-4+IL-13, respectively, and whether these effects are related. Pb did not induce cytotoxicity at any concentration in both macrophage phenotypes. In inflammatory BMDM, Pb (6 µg/dL) inhibited NO- production without affecting inducible nitric oxide synthase (iNOS) levels or basal arginase activity. At 3 and 6 µg/dL, Pb enhanced the major histocompatibility complex class II (MHC II) membrane expression but did not modify CD86 expression, TNFα, or IL-1ß production and secretion. In anti-inflammatory BMDM, Pb did not alter arginase activity, but at 3 and 6 µg/dL, increased TGF-ß1 and mannose receptor expression. Results showed that environmentally relevant concentrations of Pb alter functional outcomes or phenotypic markers of anti-inflammatory for the first time. The Pb effects on the inflammatory macrophages are not dependent on negative feedback resulting from the Pb effect on the anti-inflammatory phenotype. The Pb affected only some molecules or specific pathways related to both phenotypes. These effects could be related to Pb effects on immune defense against intracellular pathogens and allergy susceptibility.

Blood lead levels in Peruvian adults are associated with proximity to mining and DNA methylation.

BACKGROUND: Inorganic lead (Pb) is common in the environment, and is toxic to neurological, renal, and cardiovascular systems. Pb exposure influences the epigenome with documented effects on DNA methylation (DNAm). We assessed the impact of low levels of Pb exposure on DNAm among non-miner individuals from two locations in Peru: Lima, the capital, and Cerro de Pasco, a highland mining town, to study the effects of Pb exposure on physiological outcomes and DNAm. METHODS: Pb levels were measured in whole blood (n = 305). Blood leukocyte DNAm was determined for 90 DNA samples using the Illumina MethylationEPIC chip. An epigenome-wide association study was performed to assess the relationship between Pb and DNAm. RESULTS: Individuals from Cerro de Pasco had higher Pb than individuals from Lima (p-value = 2.00E-16). Males had higher Pb than females (p-value = 2.36E-04). Pb was positively associated with hemoglobin (p-value = 8.60E-04). In Cerro de Pasco, blood Pb decreased with the distance from the mine (p-value = 0.04), and association with soil Pb was approaching significance (p-value = 0.08). We identified differentially methylated positions (DMPs) associated with genes SOX18, ZMIZ1, and KDM1A linked to neurological function. We also found 45 differentially methylated regions (DMRs), seven of which were associated with genes involved in metal ion binding and nine to neurological function and development. CONCLUSIONS: Our results demonstrate that even low levels of Pb can have a significant impact on the body including changes to DNAm. We report associations between Pb and hemoglobin, Pb and distance from mining, and between blood and soil Pb. We also report associations between loci- and region-specific DNAm and Pb.

Lead (Pb) exposure is associated with changes in the expression levels of circulating miRNAS (miR-155, miR-126) in Mexican women.

The environmental contamination with lead (Pb) is considered a critical issue worldwide. Therefore, this study aimed to evaluate the expression levels of circulating miRNAs (miR-155, miR-126, and miR-145) in Mexican women exposed to Pb. Blood lead levels (BLL) were assessed in enrolled women (n = 190) using an atomic absorption method. Also, serum miRNAs expression levels were quantified through a real-time PCR assay. A mean BLL of 10.5 ± 4.50 µg/dL was detected. Overexpression of miR-155 was detected in highly exposed women. Besides, a significant simple positive relationship (p < 0.05) was found between BLL and serum miR-155 expression levels. Additionally, a significant inverse correlation (p < 0.05) was determined between BLL and serum miR-126 expression levels, as downregulation of miR-126 expression levels was observed in highly exposed women. The findings in this study are the concern, as epigenetic changes detected may represent a connection between health illnesses and Pb exposure.

Tolerance evaluation and morphophysiological responses of Astronium graveolens, a native brazilian Cerrado, to addition of lead in soil.

Since the ecosystem is contaminated by lead, decontamination is a difficult and expensive process. Therefore, an alternative would be the use of phytoremediation plants, which have been studied more intensely in recent decades. Astronium graveolens Jacq (Anacardiaceae) is a Cerrado native species and plants of this biome are known to present adaptations and modifications that keep them in this ecosystem. Our aim was to find the tolerance index of A. graveolens to lead doses and to evaluate the morphophysiological alterations of the species when exposed to the heavy metal. The experiment was carried out in a greenhouse in Ilha Solteira-SP, with a completely randomized design and using lead acetate (Pb(C2H3O2)2) as the source of the heavy metal. Samples of the vegetative organs (roots and leaves) were fixed, subsequently dehydrated in an ethyl series, included in hydroxyethyl methacrylate (Leica Historesin) and sectioned for histological slide assembly and subsequent anatomical analysis. The levels of phenolic compounds, protein, amino acid, ammonia, allantoic acid and allantoin were quantified. We calculated the tolerance index for the species. Significant differences were found in leaf and root tissues anatomy, while in relation to the physiology of A. graveolens, a significant difference was observed when the concentration of total ureids in the roots was evaluated. Pb did not interfere with the survivability of the species. In fact, A. graveolens showed a higher secondary growth in the treatment with higher level of lead.

Does Involving Parents in Soil Sampling Identify Causes of Child Exposure to Lead? A Case Study of Community Engagement in Mining-Impacted Towns in Peru.

Over a million people in Peru may be exposed to lead (Pb) due to past or present mining-related activities; however, neither soil Pb nor blood Pb are routinely monitored throughout the country. Because little is known about Pb contamination in smaller mining-impacted towns, soil Pb was mapped in four such towns with a portable X-ray fluorescence analyzer in 2015. The roadside mapping delineated hotspots of highly contaminated soil (1,000-6,000 mg/kg Pb) in two of the towns. The local health department, provided with a LeadCare II analyzer, then measured blood-Pb levels >5 in 65% and >10 µg/dL in 15% of children (n = 200) up to 6 years of age in these same four communities. There were no clear relations between child blood-Pb levels and Pb levels in soil samples collected inside (n = 50) or outside the home (n = 50). Increased child blood Pb was associated with decreased level of cleanliness of parent clothing (n = 136) and shoes (n = 138), linking a possible behavioral factor for transferring contaminated soil and dust to children. In order to explore individual exposure and variations in soil Pb, 10 parents of children with blood Pb >10 µg/dL and 10 parents of children with blood Pb <5 µg/dL were invited to collect soil samples in areas where their children play and screen it for Pb using a color-based field procedure. Importantly, parents identified a new hotspot of Pb contamination that had been missed by the previous portable X-ray fluorescence soil mapping. The findings highlight the feasibility and value of involving families impacted by environmental contamination to identify and reduce environmental health risk.