Abstract P099: Association Between Arsenic And Heart Failure

Circulation ◽  
2016 ◽  
Vol 133 (suppl_1) ◽  
Author(s):  
Kalaivani Sivakumar ◽  
Demilade Adedinsewo ◽  
Anekwe Onwuanyi
Keyword(s):  
Heart Failure ◽  
Inorganic Arsenic ◽  
Rice Flour ◽  
Arsenic Species ◽  
The United States ◽  
Dimethylarsinic Acid ◽  
Urinary Arsenic ◽  
Monomethylarsonic Acid ◽  
Developing Heart ◽  
High Arsenic

Background: Heart failure is a major contributor to morbidity and mortality in the United States. Arsenic, a ubiquitous element, found in drinking water, rice, flour and other grains, has been shown to play a role in the development of arrhythmias and coronary heart disease through vascular endothelial dysfunction and free radical injury. Studies have shown that arsenic induces interstitial myocardial fibrosis and we hypothesize that this may contribute to the development of heart failure. Methods: We conducted an analysis of the National Health and Nutrition Examination Survey (NHANES) 2011-2012. Urinary arsenic was evaluated as a combination of inorganic arsenic, and methylated arsenic species (Monomethylarsonic acid and Dimethylarsinic acid) in microgram per gram of urine creatinine. We used a logistic regression model to evaluate the relationship between quartiles of urinary arsenic and heart failure while controlling for confounders. Analyses were conducted using SAS survey procedures and data evaluated at α=0.05. Results: The total number of study participants were 2065 adults with the mean age of 40.2 years, approximately half were male (48.8%) and 64.1% were white. There was no significant association between urinary arsenic measures and incidence of heart failure. Persons with high arsenic levels (>75th percentile) were less likely to develop heart failure after controlling for confounders. Conclusion: Our results show a statistically significant decrease in the odds of developing heart failure among persons with high arsenic levels (>24ug/g). This is in contrast to other studies, which have shown high arsenic levels to have a toxic effect on the heart. Limitations of our study include the inability to determine the chronicity of exposure and exclude persons with increased levels of organic arsenic from seafood, which are nontoxic. Additional observational and prospective studies are needed to further evaluate this association.

scholarly journals Effect of arsenosugar ingestion on urinary arsenic speciation

1998 ◽  
Vol 44 (3) ◽  
pp. 539-550 ◽  
Author(s):  
Mingsheng Ma ◽  
X Chris Le
Keyword(s):  
Arsenic Speciation ◽  
Inorganic Arsenic ◽  
Sample Pretreatment ◽  
Arsenic Species ◽  
Urine Samples ◽  
Standard Reference Materials ◽  
Dimethylarsinic Acid ◽  
Urinary Arsenic ◽  
Biomarkers Of Exposure

Abstract We developed and evaluated a method for the determination of μg/L concentrations of individual arsenic species in urine samples. We have mainly studied arsenite [As(III)], arsenate [As(V)], monomethylarsonic acid (MMAA), and dimethylarsinic acid (DMAA) because these are the most commonly used biomarkers of exposure by the general population to inorganic arsenic and because of concerns over these arsenic species on their toxicity and carcinogenicity. We have also detected five unidentified urinary arsenic species resulting from the metabolism of arsenosugars. We combined ion pair liquid chromatography with on-line hydride generation and subsequent atomic fluorescence detection (HPLC/HGAFS). Detection limits, determined as three times the standard deviation of the baseline noise, are 0.8, 1.2, 0.7, and 1.0 μ/L arsenic for arsenite, arsenate, MMAA, and DMAA, respectively. These correspond to 16, 24, 14, and 20 pg of arsenic, respectively, for a 20-μL sample injected for analysis. The excellent detection limit enabled us to determine trace concentrations of arsenic species in urine samples from healthy subjects who did not have excess exposure to arsenic. There was no need for any sample pretreatment step. We used Standard Reference Materials, containing both normal and increased concentrations of arsenic, to validate the method. Interlaboratory studies with independent techniques also confirmed the results obtained with the HPLC/HGAFS method. We demonstrated an application of the method to the determination of arsenic species in urine samples after the ingestion of seaweed by four volunteers. We observed substantial increases of DMAA concentrations in the samples collected from the volunteers after the consumption of seaweed. The increase of urinary DMAA concentration is due to the metabolism of arsenosugars that are present in the seaweed. Our results suggest that the commonly used biomarkers of exposure to inorganic arsenic, based on the measurement of arsenite, arsenate, MMAA, and DMAA, are not reliable when arsenosugars are ingested from the diet.

Evaluation of Arsenate Content of Rice and Rice Bran Purchased from Local Markets in the People's Republic of China

2014 ◽  
Vol 77 (4) ◽  
pp. 665-669 ◽  
Author(s):  
SHOUHUI DAI ◽  
HUI YANG ◽  
XUEFEI MAO ◽  
JING QIU ◽  
QUANJI LIU ◽  
...  
Keyword(s):  
Rice Bran ◽  
Inorganic Arsenic ◽  
Arsenic Species ◽  
Dimethylarsinic Acid ◽  
Total Arsenic ◽  
People's Republic Of China ◽  
Local Markets ◽  
Republic Of China ◽  
Monomethylarsonic Acid ◽  
The Difference

In previous studies, inorganic arsenic and total arsenic concentrations in rice bran have been much higher than those in polished rice obtained from the same whole paddy rice. However, the arsenic species distribution between rice and bran is still unknown, especially for arsenite (AsIII) and arsenate (AsV). To characterize the arsenic species in rice and bran and explain the elevated concentrations of inorganic arsenic and total arsenic, four arsenic species, AsIII, AsV, dimethylarsinic acid, and monomethylarsonic acid, were evaluated. Rice and bran samples (n = 108) purchased from local markets in the People's Republic of China were analyzed using high-performance liquid chromatography with hydride generation and atomic fluorescence spectrometry and then microwave extraction. As expected, most of the arsenic was found in bran, with bran/rice ratios of 6.8 for total arsenic species and 6.4 for inorganic arsenic. Among four arsenic species, the maximum bran/rice ratio was 104.7 (335/3.2 μg kg−1) for AsV followed by 1.2 (69.2/56.1) for AsIII, 1.3 (6.7/5.2) for dimethylarsinic acid, and 4.0 (0.8/0.2) for monomethylarsonic acid. Thus, the large difference in arsenic concentration between rice and bran was mostly due to the difference in the AsV concentration, which account for 96 and 95% of the difference for total arsenic species and inorganic arsenic, respectively. Therefore, the possibility of AsV contamination in rice bran and its by-products needs more study. This study is the first in which concentrations of AsIII and AsV in rice and bran have been documented, revealing that a higher percentage of AsV occurs in bran than in rice.

Arsenic Speciation in Urine from Humans Intoxicated by Inorganic Arsenic Compounds

1985 ◽  
Vol 4 (2) ◽  
pp. 203-214 ◽  
Author(s):  
M.A. Lovell ◽  
J.G. Farmer
Keyword(s):  
Arsenic Trioxide ◽  
Suicide Attempts ◽  
Human Subjects ◽  
Arsenic Speciation ◽  
Inorganic Arsenic ◽  
Arsenic Species ◽  
Dimethylarsinic Acid ◽  
Monomethylarsonic Acid ◽  
Detoxification Mechanism

Trends in the urinary concentrations of the four arsenic species, pentavalent [As (V)] and trivalent [As (III)] inorganic arsenic, monomethylarsonic acid (MMAA) and dimethylarsinic acid (DMAA), were followed for several days subsequent to the acute intoxication of two human subjects by arsenic trioxide [As (III)2O3] and sodium orthoarsenate [Na2HAs(V)O4.7H2O], respectively, in unsuccessful suicide attempts. Total arsenic concentrations ranged from 1.6 to 18.7 mg/l. The increasing predominance of the less toxic methylated species, especially DMAA, after 3 or 4 days supports the concept of methylation as a natural detoxification mechanism as part of an overall reduction/methylation sequence involved in the biotransformation of inorganic arsenic by the human body. However, the additional possibility of oxidation of As(III) to As(V) in vivo under extreme immediate postingestion conditions is suggested by initial high urinary As(V) after arsenic trioxide intoxication. Relative proportions of As(V), As(III), MMAA and DMAA in both cases probably reflect species-dependent differences in rates of direct elimination and reactivity with tissues as well as the efficiency of methylation.

scholarly journals Urinary Arsenic Species are Detectable in Urban Underserved Hispanic/Latino Populations: A Pilot Study from the Study of Latinos: Nutrition & Physical Activity Assessment Study (SOLNAS)

2020 ◽  
Vol 17 (7) ◽  
pp. 2247
Author(s):  
H. Dean Hosgood ◽  
Vesna Slavkovich ◽  
Simin Hua ◽  
Madelyn Klugman ◽  
Maria Grau-Perez ◽  
...  
Keyword(s):  
Physical Activity ◽  
Pilot Study ◽  
Arsenic Species ◽  
The United States ◽  
Dimethylarsinic Acid ◽  
Physical Activity Assessment ◽  
Urinary Arsenic ◽  
Activity Assessment ◽  
Assessment Study ◽  
Urinary Arsenic Species

Background: Hispanics/Latinos represent >15% of the United States (US) population and experience a high burden of cardiovascular disease (CVD) and diabetes. Dietary exposure, particularly to arsenic (As), may be associated with CVD and diabetes in Hispanics/Latinos. Rural populations in the US exposed to As in drinking water have increased risk of diabetes and CVD; however, little is known about the risk among urban populations with low As in water who are mostly exposed to As through food. Methods: To explore the levels of inorganic arsenic exposure (the sum of inorganic and methylated arsenic species in urine, ∑As, corrected by a residual-based method) in persons of Hispanic/Latino origin, we conducted a pilot study quantifying urinary arsenic levels among 45 participants in the Study of Latinos: Nutrition & Physical Activity Assessment Study (SOLNAS). Results: The median (interquartile range) of the urinary arsenic species (µg/L) were as follows: inorganic As 0.6 (0.4, 1.0), monomethylarsonic acid 1.2 (0.7, 1.9), dimethylarsinic acid 7.2 (4.3, 15.3), and ∑As 6.0 (4.3, 10.5). Conclusions: This study adds to the existing evidence that harmful forms of arsenic are present in this group of Hispanics/Latinos.

scholarly journals Arsenic Methyltransferase and Methylation of Inorganic Arsenic

Biomolecules ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 1351
Author(s):  
Nirmal K. Roy ◽  
Anthony Murphy ◽  
Max Costa
Keyword(s):  
Oxidative Stress ◽  
Skin Color ◽  
Arsenic Exposure ◽  
Inorganic Arsenic ◽  
Arsenic Species ◽  
Amino Acid Sequences ◽  
Health Concern ◽  
Dimethylarsinic Acid ◽  
Nucleotide Polymorphisms ◽  
Foot Disease

Arsenic occurs naturally in the environment, and exists predominantly as inorganic arsenite (As (III) and arsenate As (V)). Arsenic contamination of drinking water has long been recognized as a major global health concern. Arsenic exposure causes changes in skin color and lesions, and more severe health conditions such as black foot disease as well as various cancers originating in the lungs, skin, and bladder. In order to efficiently metabolize and excrete arsenic, it is methylated to monomethylarsonic and dimethylarsinic acid. One single enzyme, arsenic methyltransferase (AS3MT) is responsible for generating both metabolites. AS3MT has been purified from several mammalian and nonmammalian species, and its mRNA sequences were determined from amino acid sequences. With the advent of genome technology, mRNA sequences of AS3MT have been predicted from many species throughout the animal kingdom. Horizontal gene transfer had been postulated for this gene through phylogenetic studies, which suggests the importance of this gene in appropriately handling arsenic exposures in various organisms. An altered ability to methylate arsenic is dependent on specific single nucleotide polymorphisms (SNPs) in AS3MT. Reduced AS3MT activity resulting in poor metabolism of iAs has been shown to reduce expression of the tumor suppressor gene, p16, which is a potential pathway in arsenic carcinogenesis. Arsenic is also known to induce oxidative stress in cells. However, the presence of antioxidant response elements (AREs) in the promoter sequences of AS3MT in several species does not correlate with the ability to methylate arsenic. ARE elements are known to bind NRF2 and induce antioxidant enzymes to combat oxidative stress. NRF2 may be partly responsible for the biotransformation of iAs and the generation of methylated arsenic species via AS3MT. In this article, arsenic metabolism, excretion, and toxicity, a discussion of the AS3MT gene and its evolutionary history, and DNA methylation resulting from arsenic exposure have been reviewed.

scholarly journals Pharmacokinetic Properties of Arsenic Species after Intravenous and Intragastrical Administration of Arsenic Trioxide Solution in Cynomolgus Macaques Using HPLC-ICP-MS

Molecules ◽  
2019 ◽  
Vol 24 (2) ◽  
pp. 241 ◽  
Author(s):  
Qiaoli Shi ◽  
Mingyan Ju ◽  
Xiaoxia Zhu ◽  
Hui Gan ◽  
Ruolan Gu ◽  
...  
Keyword(s):  
Arsenic Trioxide ◽  
Inductively Coupled Plasma ◽  
High Performance ◽  
Cynomolgus Macaque ◽  
Arsenic Species ◽  
Dimethylarsinic Acid ◽  
Inductively Coupled ◽  
Monomethylarsonic Acid ◽  
Icp Ms ◽  
Plasma Mass Spectrometry

A rapid and sensitive method was established for arsenic (As) speciation based on high performance liquid chromatography coupled to inductively coupled plasma mass spectrometry (HPLC-ICP-MS). This method was validated for the quantification of four arsenic species, including arsenite (AsIII), arsenate (AsV), monomethylarsonic acid (MMAV) and dimethylarsinic acid (DMAV) in cynomolgus macaque plasma. Separation was achieved in just 3.7 min with an alkyl reverse phase column and highly aqueous mobile phase containing 20 mM citric acid and 5 mM sodium hexanesulfonate (pH = 4.3). The calibration curves were linear over the range of 5–500 ng·mL−1 (measured as As), with r > 0.99. The above method was validated for selectivity, precision, accuracy, matrix effect, recovery, carryover effect and stability, and applied in a comparative pharmacokinetic study of arsenic species in cynomolgus macaque samples following intravenous and intragastrical administration of arsenic trioxide solution (0.80 mg·kg−1; 0.61 mg·kg−1 of arsenic); in addition, the absolute oral bioavailability of the active ingredient AsIII of arsenic trioxide in cynomolgus macaque samples was derived as 60.9 ± 16.1%.

scholarly journals Microbial Methylation of Metalloids: Arsenic, Antimony, and Bismuth

2002 ◽  
Vol 66 (2) ◽  
pp. 250-271 ◽  
Author(s):  
Ronald Bentley ◽  
Thomas G. Chasteen
Keyword(s):  
Public Health ◽  
Anaerobic Bacteria ◽  
Public Health Problem ◽  
Inorganic Arsenic ◽  
Arsenic Species ◽  
Dimethylarsinic Acid ◽  
Microbial Conversion ◽  
Microbiological Test ◽  
Methylarsonic Acid ◽  
Microbial Methylation

SUMMARY A significant 19th century public health problem was that the inhabitants of many houses containing wallpaper decorated with green arsenical pigments experienced illness and death. The problem was caused by certain fungi that grew in the presence of inorganic arsenic to form a toxic, garlic-odored gas. The garlic odor was actually put to use in a very delicate microbiological test for arsenic. In 1933, the gas was shown to be trimethylarsine. It was not until 1971 that arsenic methylation by bacteria was demonstrated. Further research in biomethylation has been facilitated by the development of delicate techniques for the determination of arsenic species. As described in this review, many microorganisms (bacteria, fungi, and yeasts) and animals are now known to biomethylate arsenic, forming both volatile (e.g., methylarsines) and nonvolatile (e.g., methylarsonic acid and dimethylarsinic acid) compounds. The enzymatic mechanisms for this biomethylation are discussed. The microbial conversion of sodium arsenate to trimethylarsine proceeds by alternate reduction and methylation steps, with S-adenosylmethionine as the usual methyl donor. Thiols have important roles in the reductions. In anaerobic bacteria, methylcobalamin may be the donor. The other metalloid elements of the periodic table group 15, antimony and bismuth, also undergo biomethylation to some extent. Trimethylstibine formation by microorganisms is now well established, but this process apparently does not occur in animals. Formation of trimethylbismuth by microorganisms has been reported in a few cases. Microbial methylation plays important roles in the biogeochemical cycling of these metalloid elements and possibly in their detoxification. The wheel has come full circle, and public health considerations are again important.

Systemic uptake of inhaled arsenic in rabbits

2002 ◽  
Vol 21 (4) ◽  
pp. 205-215 ◽  
Author(s):  
B D Beck ◽  
T M Slayton ◽  
C H Farr ◽  
D W Sved ◽  
E A Crecelius ◽  
...  
Keyword(s):  
Plasma Levels ◽  
Body Burden ◽  
Inorganic Arsenic ◽  
Dimethylarsinic Acid ◽  
Monomethylarsonic Acid ◽  
Exposure Levels ◽  
Males And Females ◽  
Four Levels ◽  
Arsenic Metabolites ◽  
Plasma Measurements

Human occupational exposure to sufficiently high levels of arsenic in air has been associated with lung cancer, but generally not other types of cancer. Thus, a better understanding of the relationship between airborne arsenic exposures and systemic uptake is essential. In this study, rabbits were exposed to one of four levels of arsenic trioxide in air for 8 h/day, 7 days/week, for 8 weeks (0.05, 0.1, 0.22, or 1.1 mg/m3). Plasma levels of inorganic arsenic, monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) were measured following the last exposure. Although there was a dose-related increase in plasma levels of methylated arsenic metabolites, statistically significant increases in mean inorganic arsenic levels in plasma were observed only in male rabbits exposed to 0.22 mg/m3, and in both males and females exposed to 1.1 mg/m3. Mean inorganic arsenic levels in plasma in males and females exposed to 0.05 and 0.1 mg/m3, and females exposed to 0.22 mg/m3, were not significantly elevated compared to controls. These results suggest that arsenic inhalation has a negligible impact on body burden of inorganic arsenic until air levels are significantly elevated. Based on plasma measurements of inorganic arsenic, the two lowest exposure levels in this study (0.05 and 0.1 mg/m3) are indistinguishable from background.

scholarly journals Control of cytokinesis by β-adrenergic receptors indicates an approach for regulating cardiomyocyte endowment

2019 ◽  
Vol 11 (513) ◽  
pp. eaaw6419 ◽  
Author(s):  
Honghai Liu ◽  
Cheng-Hai Zhang ◽  
Niyatie Ammanamanchi ◽  
Sangita Suresh ◽  
Christopher Lewarchik ◽  
...  
Keyword(s):  
Heart Failure ◽  
Adrenergic Receptors ◽  
Transcriptional Profiling ◽  
Pulmonary Stenosis ◽  
Underlying Mechanism ◽  
The United States ◽  
Heart Tissue ◽  
Developing Heart ◽  
Β Adrenergic Receptors

One million patients with congenital heart disease (CHD) live in the United States. They have a lifelong risk of developing heart failure. Current concepts do not sufficiently address mechanisms of heart failure development specifically for these patients. Here, analysis of heart tissue from an infant with tetralogy of Fallot with pulmonary stenosis (ToF/PS) labeled with isotope-tagged thymidine demonstrated that cardiomyocyte cytokinesis failure is increased in this common form of CHD. We used single-cell transcriptional profiling to discover that the underlying mechanism of cytokinesis failure is repression of the cytokinesis gene ECT2, downstream of β-adrenergic receptors (β-ARs). Inactivation of the β-AR genes and administration of the β-blocker propranolol increased cardiomyocyte division in neonatal mice, which increased the number of cardiomyocytes (endowment) and conferred benefit after myocardial infarction in adults. Propranolol enabled the division of ToF/PS cardiomyocytes in vitro. These results suggest that β-blockers could be evaluated for increasing cardiomyocyte division in patients with ToF/PS and other types of CHD.

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