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1.
Toxicol Appl Pharmacol ; 484: 116858, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38341105

RESUMO

Chronic arsenic exposures are associated with multiple hematologic disturbances, including anemia. The goal of this study was to evaluate associations between arsenic exposures and hematological parameters among men and women who are chronically exposed to elevated levels of arsenic from drinking water. Hematologic analyses were performed on blood collected from 755 participants (45% male and 54% female) in the Health Effects of Arsenic Longitudinal Study (HEALS) cohort, Bangladesh. Herein, we used linear regression models to estimate associations between red blood cell (RBC) parameters (i.e., RBC counts, hematocrit (HCT), hemoglobin (Hgb), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC)) and measurements of arsenic exposure (urinary arsenic and urinary arsenic metabolites). Arsenic exposures showed trending associations with decreased RBC counts in both men and women, a positive association with MCV in males, and an inverse association with MCHC among males, but not among non-smoking females. Among men, those who smoked had stronger associations between arsenic exposures and MCHC than non-smoking males. Collectively, our results show that arsenic exposures affect multiple RBC parameters and highlight potentially important sex differences in arsenic-induced hematotoxicity.


Assuntos
Arsênio , Adulto , Feminino , Humanos , Masculino , Arsênio/toxicidade , Estudos Longitudinais , Bangladesh/epidemiologia , Eritrócitos , Índices de Eritrócitos
2.
Toxicol Appl Pharmacol ; 384: 114783, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31669812

RESUMO

In a cohort of approximately 200 Bangladeshi men, equally divided into smokers and non-smokers and equally divided by exposure to high and low levels of drinking water arsenic, we examined ex vivo a series of immune markers and immune function tests in peripheral blood mononuclear cells (PBMC). These immune parameters included PBMC cell surface markers (CSM) for B, T, monocytes, and NK cells, activated T and B cell markers, cytokine production in vitro, and analysis of CD4 subsets (Th1, Th2, Treg, and Th17 cells). We found that the effects of cigarette smoke were quite different than those associated with arsenic or polycyclic aromatic hydrocarbon (PAH)-DNA adducts. Cigarette smoking was associated with a significant increase in the number of PAH-DNA adducts as well as an increase in urinary levels of 1-hydropxypyrene (1-OHP). After correcting for arsenic exposure and PAH-DNA adducts, we found that cigarette smoking was associated with an increase in the percentage of CD19+ B cells, as well as the percentage of activated B cells (CD19+, HLA-DRbright cells) found in PBMC. These findings demonstrate activation of the immune system during chronic exposure to cigarette smoke, which is a known risk factor for autoimmune diseases.


Assuntos
Doenças Autoimunes/epidemiologia , Linfócitos B/imunologia , Fumar Cigarros/efeitos adversos , Adutos de DNA/efeitos dos fármacos , Antígenos HLA-DR/imunologia , Adolescente , Adulto , Idoso , Doenças Autoimunes/imunologia , Linfócitos B/efeitos dos fármacos , Bangladesh , Fumar Cigarros/sangue , Fumar Cigarros/imunologia , Estudos de Coortes , Adutos de DNA/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Fatores de Risco , Fumaça/efeitos adversos , Nicotiana/efeitos adversos , Adulto Jovem
3.
Toxicol Appl Pharmacol ; 331: 62-68, 2017 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-28526635

RESUMO

Drinking water arsenic (WAs) exposure has been linked to a number of detrimental health outcomes including anemia, primarily among pregnant women. Little is known about the effects of arsenic (As) on hematological disorders among men. We have examined the role of As exposure on hematological indicators of anemia in a group of men exposed to a wide range of As in their drinking water. We conducted a cross-sectional investigation among 119 healthy men in the Health Effects of As Longitudinal Study (HEALS) cohort, in rural Bangladesh. The participants are part of an ongoing study focused on evaluating the influence of As and smoking on immune function. Samples were collected at recruitment and analyzed for water As, urinary As (UAs) and UAs metabolites to assess As exposure. Blood samples were also collected at recruitment and assayed immediately for hematological parameters. We found that increased WAs levels were associated with decreased red blood cell counts [ß=-0.13, p<0.0001] as well as hematocrit packed cell volumes [ß=-0.68, p=0.008] following adjustment for age, smoking, body mass index and polycyclic aromatic hydrocarbon-DNA adducts. Other measures of As exposure (UAs and its metabolites) demonstrated similar associations. Slightly stronger effects were observed among smokers. We also observed an effect of As on hemoglobin among smokers in relation to UAs [ß=-0.54, p<0.05]. Our analysis revealed effects of As exposure on hematological indicators of anemia in a group of healthy male smokers and non-smokers.


Assuntos
Anemia/induzido quimicamente , Anemia/epidemiologia , Arsênio/toxicidade , Água Potável/efeitos adversos , Exposição Ambiental/efeitos adversos , Fumar/epidemiologia , Adulto , Idoso , Anemia/sangue , Arsênio/administração & dosagem , Bangladesh/epidemiologia , Estudos de Coortes , Estudos Transversais , Relação Dose-Resposta a Droga , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fumar/sangue , Poluentes Químicos da Água/efeitos adversos , Poluentes Químicos da Água/sangue
4.
Cureus ; 16(7): e63619, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39092370

RESUMO

Ectopic adrenocorticotropic secretion (EAS) is classically related to small-cell lung cancer but is caused by a wide variety of tumors. In approximately one-fifth of cases, the cause remains unidentified. Excess adrenocorticotropic hormone (ACTH) leads to Cushing's syndrome, and the presentation can be due to biochemical derangements such as hypokalemia and hyperglycemia. Alternatively, it may manifest with secondary symptoms such as weight gain, hypertension, skin thinning, abdominal striae, and/or psychotic manifestations. The diagnosis is established through dynamic testing after confirming excess cortisol and ACTH levels. Imaging is then used to identify the hormonally active lesion. Controlling hypercortisolism with steroidogenesis inhibitors is the initial step before proceeding to definitive treatment. Ideally, tumor resection, if possible, but bilateral adrenalectomies are considered in cases not amenable to curative surgery.

5.
PLoS One ; 17(4): e0266168, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35404942

RESUMO

There is limited evidence on the effects of environmental exposure to arsenic (As) on the immune system in adults. In a population-based study, we have found that urinary As (UAs), and its metabolites [inorganic As (InAs), monomethylated arsenicals (MMA+3/+5), and dimethylated arsenicals (DMA+3/+5)] modulate or influence the number of T-helper 17 (Th17) cells and IL-17A cytokine production. In non-smoking women, we observed that UAs and DMA+3/+5 were associated with changes in Th17 cell numbers in a nonlinear fashion. In smoking males, we found that UAs was associated with a significant decrease of Th17 cell numbers. Similar association was observed among non-smoking males. Likewise, UAs, DMA+3/+5 and MMA+3/+5 were associated with diminished production of IL-17A among non-smoking males. When stratified by Vitamin D levels defined as sufficient (≥20 ng/ml) and insufficient (<20 ng/ml), we found a substancial decrease in Th17 cell numbers among those with insufficient levels. Individuals with sufficient VitD levels demonstrated significant inhibition of IL-17A production in non-smoking males. Collectively, we find that exposure to As via drinking water is associated with alterations in Th17 numbers and IL-17A production, and that these associations may be modified by Vitamin D status. Our findings have significance for health outcomes associated with As exposure.


Assuntos
Arsênio , Arsenicais , Adulto , Arsênio/análise , Exposição Ambiental/efeitos adversos , Feminino , Humanos , Interleucina-17 , Leucócitos Mononucleares/metabolismo , Masculino , Células Th17/metabolismo , Vitamina D/farmacologia , Vitaminas
6.
PLoS One ; 15(6): e0234965, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32574193

RESUMO

There are limited data examining the consequences of environmental exposure to arsenic on the immune system in adults, particularly among smokers. Smoking has been shown to exacerbate or contribute to impaired immune function in men chronically exposed to arsenic. In contrast, vitamin D (VitD) is known to have a positive influence on innate and adaptive immune responses. The effect of circulating VitD on arsenic-associated immune dysfunction is not known. Here we examine the relationship of arsenic exposure and T cell proliferation (TCP), a measure of immune responsiveness, and circulating VitD among adult men and women in Bangladesh. Arsenic exposure was assessed using total urinary arsenic as well as urinary arsenic metabolites all adjusted for urinary creatinine. TCP was measured ex vivo in cryopreserved peripheral blood mononuclear cells from 614 adult participants enrolled in the Bangladesh Health Effects of Arsenic Longitudinal Study; serum VitD was also evaluated. The influence of cigarette smoking on arsenic-induced TCP modulation was assessed only in males as there was an inadequate number of female smokers. These studies show that arsenic suppressed TCP in males. The association was significantly strong in male smokers and to a lesser extent in male non-smokers. Interestingly, we found a strong protective effect of high/sufficient serum VitD levels on TCP among non-smoking males. Furthermore, among male smokers with low serum VitD (⊔20 ng/ml), we found a strong suppression of TCP by arsenic. On the other hand, high VitD (>20 ng/ml) was found to attenuate effects of arsenic on TCP among male-smokers. Overall, we found a strong protective effect of VitD, when serum levels were >20 ng/ml, on arsenic-induced inhibition of TCP in men, irrespective of smoking status. To our knowledge this is the first large study of immune function in healthy adult males and females with a history of chronic arsenic exposure.


Assuntos
Arsênio/toxicidade , Exposição Ambiental/efeitos adversos , Fumar/imunologia , Linfócitos T/efeitos dos fármacos , Vitamina D/sangue , Adulto , Idoso , Arsênio/urina , Bangladesh/epidemiologia , Proliferação de Células/efeitos dos fármacos , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Fumar/sangue , Fumar/epidemiologia , Linfócitos T/imunologia , Vitamina D/imunologia
7.
PLoS One ; 14(5): e0216662, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31095595

RESUMO

Arsenic and polycyclic aromatic hydrocarbons (PAH) are environmental pollutants to which people around the world are exposed through water, food and air. In mouse and in vitro studies of human cells, both of these chemicals have been shown to modulate the immune system. In some experimental studies, a synergistic disruption of immune function was observed by a combined exposure to arsenic and PAH. However, a joint effect of arsenic and PAH on immune function has not been studied in humans. We have conducted an epidemiological investigation to examine effects of chronic arsenic and PAH exposures on immune function. We assessed T-cell proliferation (TCP) and cytokine production of anti-CD3/anti-CD28 stimulated lymphocytes in human peripheral blood mononuclear cells (HPBMC) among 197 healthy men enrolled to the Health Effects of Arsenic Longitudinal (HEALS) cohort in Bangladesh. By design, approximately half were active smokers and the rest were never smokers. Our analyses demonstrated that IL-1b, IL-2, IL-4 and IL-6 were significantly stimulated as a function of urinary arsenic levels in models adjusted for age, body mass index (BMI), smoking status and PAH-DNA adducts. After correcting for false detection rate (FDR), only IL-1b remained statistically significant. We found a U-shaped dose response relationship between urinary arsenic and IL-1b. On the other hand, PAH-DNA adducts were associated with an inhibition of TCP and appeared as an inverted U-shape curve. Dose response curves were non-monotonic for PAH-DNA adduct exposures and suggested that cytokine secretion of IFNg, IL-1b, IL-2, IL-10 and IL17A followed a complex pattern. In the majority of donors, there was a trend towards a decrease in cytokine associated with PAH-DNA adducts. We did not observe any interaction between urinary arsenic and PAH-DNA adducts on immune parameters. Our results indicate that long-term exposures to arsenic and PAH have independent, non-monotonic associations with TCP and cytokine production.


Assuntos
Arsênio/toxicidade , Exposição Ambiental/efeitos adversos , Imunidade/efeitos dos fármacos , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Adulto , Idoso , Animais , Bangladesh , Adutos de DNA/metabolismo , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Hidrocarbonetos Policíclicos Aromáticos/metabolismo , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia
8.
PLoS One ; 14(7): e0220451, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31365547

RESUMO

Exposures to environmental arsenic (As) and polycyclic aromatic hydrocarbons (PAH) have been shown to independently cause dysregulation of immune function. Little data exists on the associations between combined exposures to As and PAH with immunotoxicity in humans. In this work we examined associations between As and PAH exposures with lymphoid cell populations in human peripheral blood mononuclear cells (PBMC), as well as alterations in differentiation and activation of B and T cells. Two hundred men, participating in the Health Effects of Arsenic Longitudinal Study (HEALS) in Bangladesh, were selected for the present study based on their exposure to As from drinking water and their cigarette smoking status. Blood and urine samples were collected from study participants. We utilized multiparameter flow cytometry in PBMC to identify immune cells (B, T, monocytes, NK) as well as the T-helper (Th) cell subsets (Th1, Th2, Th17, and Tregs) following ex vivo activation. We did not find evidence of interactions between As and PAH exposures. However, individual exposures (As or PAH) were associated with changes to immune cell populations, including Th cell subsets. Arsenic exposure was associated with an increase in the percentage of Th cells, and dose dependent changes in monocytes, NKT cells and a monocyte subset. Within the Th cell subset we found that Arsenic exposure was also associated with a significant increase in the percentage of circulating proinflammatory Th17 cells. PAH exposure was associated with changes in T cells, monocytes and T memory (Tmem) cells and with changes in Th, Th1, Th2 and Th17 subsets all of which were non-monotonic (dose dependent). Alterations of immune cell populations caused by environmental exposures to As and PAH may result in adverse health outcomes, such as changes in systemic inflammation, immune suppression, or autoimmunity.


Assuntos
Arsênio/efeitos adversos , Exposição Ambiental/efeitos adversos , Leucócitos Mononucleares/imunologia , Hidrocarbonetos Policíclicos Aromáticos/efeitos adversos , Fumaça/efeitos adversos , Subpopulações de Linfócitos T/imunologia , Humanos , Leucócitos Mononucleares/efeitos dos fármacos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Subpopulações de Linfócitos T/efeitos dos fármacos
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