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Exposure to metals, a newly recognized risk factor for cardiovascular disease (CVD), could be related to atherosclerosis progression. The authors hypothesized that higher urinary levels of nonessential (cadmium, tungsten, uranium) and essential (cobalt, copper, zinc) metals previously associated with CVD would be associated with baseline and rate of change of coronary artery calcium (CAC) progression, a subclinical marker of CVD in MESA (Multi-Ethnic Study of Atherosclerosis). We analyzed data from 6,418 MESA participants with spot urinary metal levels at baseline (2000-2002) and 1 to 4 repeated, continuous measures of CAC over a 10-year period. We used linear mixed-effect models to assess the association of baseline urinary metal levels with baseline CAC and cumulative change in CAC over a 10-year period. Urinary metals (μg/g creatinine) and CAC were log transformed. Models were adjusted for baseline sociodemographic factors, estimated glomerular filtration rate, lifestyle factors, and clinical factors. At baseline, the median CAC was 6.3 (Q1-Q3: 0.7-58.2). Comparing the highest to lowest quartile of urinary cadmium, CAC levels were 51% (95% CI: 32%, 74%) higher at baseline and 75% (95% CI: 47%, 107%) higher over the 10-year period. For urinary tungsten, uranium, and cobalt, the corresponding CAC levels over the 10-year period were 45% (95% CI: 23%, 71%), 39% (95% CI: 17%, 64%), and 47% (95% CI: 25%, 74%) higher, respectively, with no difference for models with and without adjustment for clinical factors. For copper and zinc, the corresponding estimates dropped from 55% to 33% and from 85% to 57%, respectively, after adjustment for clinical factors. The associations of metals with CAC were comparable in magnitude to those for classical CVD risk factors. Exposure to metals was generally associated with extent of coronary calcification at baseline and follow-up. These findings support that metals are associated with the progression of atherosclerosis, potentially providing a novel strategy for the prevention and treatment of atherosclerosis progression. [ABSTRACT FROM AUTHOR]

We wish to disclose the first synthesis of 1- O -hexadecanoyl-2- O -((15-(dimethylarsinoyl)pentadecanoyl)oxy)- sn - glycero -3-phosphocholine, which belongs to the group of arsenic-containing phosphatidylcholines (AsPCs), recently discovered in herring caviar. The synthesized product will serve as a model compound to study biological and toxicological properties of arsenolipids in food. [ABSTRACT FROM AUTHOR]

Two previously unknown arsenic-containing cyclic ethers have been synthesized, namely (((2 R ,3 R ,4 S ,5 R )-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)methyl)dimethylarsine oxide and its C-1 epimer (((2 S ,3 R ,4 S ,5 R )-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)methyl)dimethylarsine oxide as its trifluoroacetate salt. The compounds serve as model compounds for a new group of unidentified arsenolipids observed in a unicellular alga and sediments. [ABSTRACT FROM AUTHOR]

[Display omitted] • Oxo-arsenic hydrocarbons are the major arsenolipids in fresh salmon. • When salmon is cooked, thioxo-arsenic hydrocarbons are formed. • Food regulations need to consider the arsenic species present in cooked fish. Arsenic hydrocarbons, major arsenolipids occurring naturally in marine fish, have substantial cytotoxicity leading to human health-related studies of their distribution and abundance in foods. These studies have all investigated fresh foods; because most fish are cooked before being consumed, it is both food- and health-relevant to determine the arsenolipids present in cooked fish. We used HPLC/mass spectrometry to investigate the arsenolipids present in salmon (Salmo salar) before and after cooking by either baking or steaming. In raw salmon (total As 2.74 mg kg−1 dry mass, of which 6% was lipid-soluble), major arsenolipids were three arsenic hydrocarbons (oxo-AsHC 332, oxo-AsHC 360, and oxo-AsHC 404, ca 55% of total arsenolipids) and a band of unidentified less-polar arsenolipids (ca 40%), trace amounts of another four arsenic hydrocarbons and two thioxo analogs were also detected. During the cooking process, 28% of the oxo-AsHCs were converted to their thioxo analogs. Our study shows that arsenic hydrocarbons naturally present in fresh fish are partly converted to their thioxo analogs during cooking by either baking or steaming. The greater lipophilicity of the thioxo analogs could alter the mode of toxicity of arsenic hydrocarbons, and hence future food regulations for arsenic should consider the influence of cooking on the precise type of arsenolipid in fish. [ABSTRACT FROM AUTHOR]

• The major arsenic species in salmon were arsenic hydrocarbons and arsenobetaine. • When the salmon was ingested by a nursing mother, arsenic hydrocarbons and arsenobetaine were rapidly transported to the milk of the mother. • The transport efficiency was 2–3 % for the arsenic hydrocarbons but only 0.03 % for arsenobetaine. We address two questions relevant to infants' exposure to potentially toxic arsenolipids, namely, are the arsenolipids naturally present in fish transported intact to a mother's milk, and what is the efficiency of this transport. We investigated the transport of arsenolipids and other arsenic species present in fish to mother's milk by analyzing the milk of a single nursing mother at 15 sampling times over a 3-day period after she had consumed a meal of salmon. Total arsenic values were obtained by elemental mass spectrometry, and arsenic species were measured by HPLC coupled to both elemental and molecular mass spectrometry. Total arsenic increased from background levels (0.1 μg As kg−1) to a peak value of 1.72 μg As kg−1 eight hours after the fish meal. The pattern for arsenolipids was similar to that of total arsenic, increasing from undetectable background levels (< 0.01 μg As kg−1) to a peak after eight hours of 0.45 μg As kg−1. Most of the remaining total arsenic in the milk was accounted for by arsenobetaine. The major arsenolipids in the salmon were arsenic hydrocarbons (AsHCs; 55 % of total arsenolipids), and these compounds were also the dominant arsenolipids in the milk where they contributed over 90 % of the total arsenolipids. Our study has shown that ca 2–3 % of arsenic hydrocarbons, natural constituents of fish, can be directly transferred unchanged to the milk of a nursing mother. In view of the potential neurotoxicity of AsHCs, the effects of these compounds on the brain developmental stage of infants need to be investigated. [ABSTRACT FROM AUTHOR]

[Display omitted] • Urinary selenium levels were associated with changes in DNA methylation. • Elastic net models selected 425 differentially methylated positions (DMPs) • The top associated site cg00163554 was annotated to the DIP2C. • The biological implications of these DMPs relative to disease must be further studied. Selenium (Se) is an essential nutrient linked to adverse health endpoints at low and high levels. The mechanisms behind these relationships remain unclear and there is a need to further understand the epigenetic impacts of Se and their relationship to disease. We investigated the association between urinary Se levels and DNA methylation (DNAm) in the Strong Heart Study (SHS), a prospective study of cardiovascular disease (CVD) among American Indians adults. Selenium concentrations were measured in urine (collected in 1989–1991) using inductively coupled plasma mass spectrometry among 1,357 participants free of CVD and diabetes. DNAm in whole blood was measured cross-sectionally using the Illumina MethylationEPIC BeadChip (850 K) Array. We used epigenome-wide robust linear regressions and elastic net to identify differentially methylated cytosine-guanine dinucleotide (CpG) sites associated with urinary Se levels. The mean (standard deviation) urinary Se concentration was 51.8 (25.1) μg/g creatinine. Across 788,368 CpG sites, five differentially methylated positions (DMP) (hypermethylated: cg00163554, cg18212762, cg11270656, and hypomethylated: cg25194720, cg00886293) were significantly associated with Se in linear regressions after accounting for multiple comparisons (false discovery rate p-value: 0.10). The top hypermethylated DMP (cg00163554) was annotated to the Disco Interacting Protein 2 Homolog C (DIP2C) gene, which relates to transcription factor binding. Elastic net models selected 425 hypo- and hyper-methylated DMPs associated with urinary Se, including three sites (cg00163554 [DIP2C], cg18212762 [ MAP4K2 ], cg11270656 [ GPIHBP1 ]) identified in linear regressions. Urinary Se was associated with minimal changes in DNAm in adults from American Indian communities across the Southwest and the Great Plains in the United States, suggesting that other mechanisms may be driving health impacts. Future analyses should explore other mechanistic biomarkers in human populations, determine these relationships prospectively, and investigate the potential role of differentially methylated sites with disease endpoints. [ABSTRACT FROM AUTHOR]

Arsenolipid concentrations were measured in 17 food composites prepared from 152 food items purchased in Shizuoka city, Japan, to (1) determine the food contributing to daily intake of arsenolipids, and (2) estimate the daily intake of arsenolipids. Analysis of arsenolipids was performed by high performance liquid chromatography-inductively coupled plasma mass spectrometry/electrospray ionization tandem mass spectrometry (HPLC-ICP-MS/ESI-MS-MS). Arsenic containing hydrocarbons (AsHCs), arsenic containing fatty acids (AsFAs), and arsenosugar phospholipids (AsSugPLs) were detected only in “algae” and “fish and shellfish” of the 17 food composites in a concentration range of 4.4–233 ng As/g fresh weight (fw). Two cytotoxic arsenolipids, AsHC332 and AsHC360, were detected in “algae” and “fish and shellfish” in the concentrations range of 33–40 ng As/g fw. The estimated average daily intake of AsHC332 and AsHC360 was ca 3000 and 360 ng As/person/day, or 50 and 6.0 ng As/kg bw/day, respectively. The present study indicated that arsenolipids from “algae” and “fish and shellfish” consumption contributed to the daily intake of toxic AsHCs, though the margin of exposure for the AsHC332 and AsHC360 does not appear to pose a health risk for the general Japanese population. [ABSTRACT FROM AUTHOR]

The previously unknown arsenic-containing triacylglycerides (AsTAGs) 3-((15-(dimethylarsinoyl)pentadecanoyl)oxy)propane-1,2-diyl dipalmitate 1 and 2-((15-(dimethylarsinoyl)pentadecanoyl)oxy)propane-1,3-diyl dipalmitate 2 have been synthesized. They will serve as model compounds in the search for naturally occurring AsTAGs, recently proposed natural constituents of fish oils. [ABSTRACT FROM AUTHOR]

• Folate and B12 supplementation increased arsenic methylation in 8–10 yr children. • Increasing arsenic methylation facilitates urinary arsenic elimination. • Nutritional interventions with folate and vitamin B12 may reduce arsenic toxicity. Inorganic arsenic is metabolized to monomethyl- (MMAs) and dimethyl- (DMAs) species via one-carbon metabolism (OCM); this facilitates urinary arsenic elimination. OCM is influenced by folate and vitamin B12 and previous randomized control trials (RCTs) showed that folic acid (FA) supplementation increases arsenic methylation in adults. This RCT investigated the effects of FA + B12 supplementation on arsenic methylation in children, a key developmental stage where OCM supports growth. A total of 240 participants (8–11 years, 53 % female) drinking from wells with arsenic concentrations > 50 μg/L, were encouraged to switch to low arsenic wells and were randomized to receive 400 μg FA + 5 μg B12 or placebo daily for 12-weeks. Urine and blood samples were collected at baseline, week 1 (only urine) and week 12. Generalized estimated equation (GEE) models were used to assess treatment effects on arsenic species in blood and urine. At baseline, the mean ± SD total blood and urinary arsenic were 5.3 ± 2.9 μg/L and 91.2 ± 89.5 μg/L. Overall, total blood and urine arsenic decreased by 11.7% and 17.6%, respectively, at the end of follow up. Compared to placebo, the supplementation group experienced a significant increase in the concentration of blood DMAs by 14.0% (95% CI 5.0, 25.0) and blood secondary methylation index (DMAs/MMAs) by 0.19 (95% CI: 0.09, 0.35) at 12 weeks. Similarly, there was a 1.62% (95% CI: 0.43, 20.83) significantly higher urinary %DMAs and −1.10% (95% CI: −1.73, −0.48) significantly lower urinary %MMAs in the supplementatio group compared to the placebo group after 1 week. The direction of the changes in the urinary %iAs, %MMAs, and %DMAs at week 12 were consistent with those at week 1, though estimates were not significant. Treatment effects were stronger among participants with higher baseline blood arsenic concentrations. Results were consistent across males and females, and participants with higher and lower folate and B12 status at baseline. This RCT confirms that FA + B12 supplementation increases arsenic methylation in children as reflected by decreased MMAs and increased DMAs in blood and urine. Nutritional interventions may improve arsenic methylation and elimination in children, potentially reducing arsenic toxicity while also improving nutritional status. [ABSTRACT FROM AUTHOR]

The As concentrations, along with 34 other elements, and the As speciation were investigated in wild-grown samples of the parasitic mushroom Tolypocladium ophioglossoides with inductively coupled plasma mass spectrometry (ICPMS) and high performance liquid chromatography coupled to ICPMS. The As concentrations were 0.070–3.44 mg kg−1 dry mass. More remarkable was the As speciation, where up to 56% of the extracted As were found to be an unknown As species, which was marginally retained under anion- and also cation-exchange conditions. After testing several different chromatographic settings, the compound was finally isolated and identified as 2-(sulfoxyethyl) trimethylarsonium ion (in short: arsenocholine- O -sulfate) with high resolution mass spectrometry. The compound was synthesized and further quantified in all investigated samples via ion-pair chromatography coupled to ICPMS. In addition to the high abundance of arsenocholine- O -sulfate in T. ophioglossoides , small amounts of this As species were also detected in one sample of the host mushroom, Elaphomyces asperulus. In a sample of another parasitic mushroom, Ophiocordyceps sinensis , arsenocholine- O -sulfate could not be detected, but the main species was another unknown compound that was oxidized to inorganic As(V) with hydrogen peroxide. This is the first discovery of arsenocholine- O -sulfate in nature. It is possible that it is present in many other organisms, at least in low concentrations, and just has not been detected there yet because of its unusual chromatographic behavior. The existence of arsenocholine- O -sulfate brings up questions again about the biotransformation pathways of As in the environment and the specific behavior of fungi. Image 1 • Arsenocholine- O -sulfate was discovered for the first time in nature. • Arsenocholine- O -sulfate was the main As species in Tolypocladium ophioglossoides. • Concentrations of As species and 35 elements were determined in T. ophioglossoides. • Hosts, Elaphomyces spp., show different elemental profiles than T. ophioglossoides. [ABSTRACT FROM AUTHOR]

Twenty one arsenolipids, including eight new compounds (AsSugPL 692, AsSugPL 706, AsSugPL 720, AsSugPL 734, AsSugPL 742, AsSugPL 746, AsSugPL 748, and AsSugPL 776) were identified in the edible brown alga Kombu, Saccharina japonica , by means of HPLC coupled with elemental and molecular mass spectrometry. The hitherto undescribed compounds are all mono-acyl arsenosugar phospholipids, differing from previously reported natural arsenic-containing phospholipids by containing only one fatty acid on the glycerol group. Collectively, this new group of mono-acyl compounds constituted about 30% of total lipid arsenic; other significant groups were the di-acyl arsenosugar phospholipids (50%) and arsenic hydrocarbons (20%). The origin and relevance of the mono-acyl arsenosugar phospholipids in Kombu, a commercial seafood product, is briefly discussed. [ABSTRACT FROM AUTHOR]