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1.
J Biochem Mol Toxicol ; 36(2): e22955, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34755932

ABSTRACT

The objective of this study was to evaluate the biomarkers of exposure to boron, nickel, arsenic, and antimony in an industrial region, evaluating the bioaccumulation in biological substrates and the correlation with biomarkers such as hematological parameters. Through indication of the accumulation of some minerals in the horse's biological substrates reflects environmental pollution. Moreover, an additional aim of the study was to show whether these contaminants have an influence on the hematological parameters in horses. Blood, serum, mane, and tail samples from 20 horses from an industrial area were analyzed to determine boron (B), nickel (Ni), arsenic (As), antimony (Sb) concentration. Hematological parameters (red blood cell [RBC], white blood cells [WBC], hemoglobin [Hb], hematocrit [Hct], mean corpuscular volume [MCV], mean corpuscular hemoglobin [MCH], mean corpuscular hemoglobin concentration [MCHC], platelet [PLT]) as a biomarker of blood in relation to the bioaccumulation of these elements were analyzed also. Descriptive statistical analysis was performed and single regression analysis (Pearson) and multiple regression analysis (p < 0.05) between blood factors, As, B, Ni, and Sb concentrations, and for each mineral in different substrate, respectively. Results showed a significant correlation between tail and mane concentrations with serum and blood for boron concentration (r = -1 p < 0.05). No significant correlation between sample (feed, hay, mane, tail, and water) concentrations and As, Ni, and Sb were found. A significantly negative correlation with blood parameters (r = -1 p < 0.05) was observed in Boron concentration for mane and tail. This suggests that the mane and tail may be a potential means to investigate suspected exposure to excessive levels of trace minerals.


Subject(s)
Antimony/blood , Boron/blood , Horses/blood , Nickel/blood , Animals , Arsenic , Biomarkers/blood , Hematocrit
2.
Ecotoxicol Environ Saf ; 221: 112420, 2021 Sep 15.
Article in English | MEDLINE | ID: mdl-34166935

ABSTRACT

Antimony is one of the heavier pnictogens and is widely found in human food chains, water sources, and as an air pollutant. Recent years have seen steadily increasing concentrations of antimony in the ecological environment; critically, several studies have indicated that antimony might pose a tumorigenic risk factor in several cancers. Therefore, antimony toxicity has attracted increasing research attention, with the molecular mechanisms underlying suspected antimony-mediated tumor transformation of greatest interest. Our results showed that the serum concentration of antimony was higher in bladder tumor patients relative to levels in non-tumor patients. Moreover, that such high antimony serum concentration were closely associated with poorer outcome in bladder tumor patients. Additionally, we demonstrated that the presence of antimony promoted both in vitro and in vivo bladder tumor cell growth. Our results also indicated that low-dose antimony resulted in significantly decreased mitochondrial membrane potential, mitochondrial respiratory enzyme complex I/II/III/IV activity, ATP/ADP ratio, and ATP concentration relative to the control group. These findings suggested that antimony caused mitochondrial damage. Finally, we found that low-dose antimony(0.8uM) inhibited mitophagy by deregulating expression of PINK1, Parkin, and p(ser65)-Parkin, and activation of PINK1-Parkin pathway by CCCP could inhibit antimony-induced tumor cell growth. Collectively, this inhibited the proliferation of bladder tumor cells. Overall, our study suggested that antimony promoted bladder tumor cell growth by inhibiting PINK1-Parkin-mediated mitophagy. These findings highlight the therapeutic potential in targeting molecules within this antimony induced-PINK1/Parkin signaling pathway and may offer a new approach for the treatment of bladder cancer.


Subject(s)
Antimony/toxicity , Environmental Pollutants/toxicity , Protein Kinases/metabolism , Ubiquitin-Protein Ligases/metabolism , Urinary Bladder Neoplasms , Animals , Antimony/blood , Cell Line, Tumor , Environmental Pollutants/blood , Humans , Membrane Potential, Mitochondrial/drug effects , Mice, Inbred BALB C , Mice, Nude , Mitophagy/drug effects , Urinary Bladder Neoplasms/blood , Urinary Bladder Neoplasms/metabolism , Urinary Bladder Neoplasms/mortality , Urinary Bladder Neoplasms/pathology
3.
Bioanalysis ; 13(8): 655-667, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33829863

ABSTRACT

Background: A high-throughput method using inductively coupled plasma mass spectrometry (ICP-MS) was developed and validated for the quantitative analysis of antimony in human plasma and peripheral blood mononuclear cells from patients with cutaneous leishmaniasis undergoing treatment with meglumine antimoniate. Materials & methods: Antimony was digested in clinical samples with 1% tetramethylammonium hydroxide/1% EDTA and indium was used as internal standard. Accuracy, precision and stability were evaluated. Conclusion: Taking the lower limit of quantitation to be the lowest validation concentration with precision and accuracy within 20%, the current assay was successfully validated from 25 to 10000 ng/ml for antimony in human plasma and peripheral blood mononuclear cells. This protocol will serve as a baseline for future analytical designs, aiming to provide a reference method to allow inter-study comparisons.


Lay abstract Cutaneous leishmaniasis is a disease caused by single-cell parasites in the genus Leishmania which results in painful skin ulcers and is spread by insect bites. Drugs containing antimony are the mainstay therapy for cutaneous leishmaniasis, but if and how the amount of these compounds in the cells can affect the success of the treatment, remains unknown. Validated methods to reliably measure these amounts in human cells are limited. Here we have developed a validated method that allows quantifying antimony in human plasma and peripheral blood cells from patients undergoing antileishmanial treatment. This protocol will serve as a baseline for future studies aiming to understand how antimonials work to treat leishmaniasis infections and how this therapy can be improved.


Subject(s)
Antimony/chemistry , Antiprotozoal Agents/pharmacokinetics , Meglumine Antimoniate/pharmacokinetics , Antimony/blood , Antiprotozoal Agents/blood , Antiprotozoal Agents/chemistry , Humans , Leishmania/drug effects , Mass Spectrometry , Meglumine Antimoniate/blood , Meglumine Antimoniate/chemistry , Molecular Structure , Parasitic Sensitivity Tests
4.
J Trace Elem Med Biol ; 62: 126602, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32650063

ABSTRACT

BACKGROUND: Exposure of toxic metals from e-cigarette use is a cause for public health concern because youth, young adults, and non-smokers are the target population rapidly adopting e-cigarette use. The purpose of this research is to determine the association of the body burden of heavy metals with e-cigarette use using NHANES (U.S.) 2015-2016 data. METHODS: Blood lead (N = 1899) and urinary cadmium, barium, and antimony (N = 1302) data were extracted from NHANES, 2015-2016; geometric means were calculated and bivariate and multivariable linear regression analyses were conducted. Participants were categorized as having neither e-cigarette nor cigarette use; smoking history (including dual use with e-cigarettes); and only e-cigarette (current or former). RESULTS: In multivariable analyses adjusted for sex, race/ethnicity, age, and poverty levels, current or former e-cigarette use failed to reach a statistical significance in the association with metals. However, participants with a smoking history were more likely to have higher blood lead and urinary cadmium than participants who neither used e-cigarettes nor cigarettes. CONCLUSION: Blood lead levels, and urinary cadmium, barium, and antimony levels were similar between participants who used e-cigarettes and participants who did not.


Subject(s)
Antimony/blood , Barium/blood , Cadmium/blood , Electronic Nicotine Delivery Systems , Lead/blood , Adult , Female , Humans , Male , Multivariate Analysis
5.
J Clin Lab Anal ; 34(7): e23269, 2020 Jul.
Article in English | MEDLINE | ID: mdl-32319138

ABSTRACT

BACKGROUND: It has been shown there is an upward trend for strontium (Sr) and antimony (Sb) levels from low-risk (LR) to high-risk (HR) areas of etiology of esophageal cancer in water, soil, and grains grown in Golestan province. In the present study, the serum levels of Sr and Sb were determined in healthy individuals living in these areas. METHODS: This cross-sectional study was performed on fasting blood serum of adult healthy individuals collected by cluster sampling. Subjects were divided into two groups, those living in either HR or LR areas. Strontium and antimony serum levels were measured using a graphite furnace atomic absorption spectroscopy. RESULTS: A total of 200 volunteers were enrolled from which 96 persons (48%) and 104 persons (52%) were from either HR or LR areas, respectively. The sex distribution was 40.9% male and 59.1% female, and the average age of enrolled people was 50.9 years. The average strontium levels were 30.44 ± 4.05 and 30.29 ± 3.74 µg/L in LR and HR, respectively. It also has been shown the average antimony levels were 15.21 ± 3.40, 14.81 ± 3.17, 15.13 ± 3.62, and 15.07 ± 3.62 µg/L in LR, HR, urban, and rural populations, respectively. CONCLUSION: The serum levels of strontium and antimony were not significantly different in healthy adults living in high- and low-risk areas of esophageal cancer. However, the average antimony serum levels in Golestan Province were above the reference interval in different countries.


Subject(s)
Antimony/blood , Esophageal Neoplasms/epidemiology , Strontium/blood , Adult , Cross-Sectional Studies , Esophageal Neoplasms/blood , Female , Humans , Iran/epidemiology , Male , Middle Aged , Risk Factors , Spectrophotometry, Atomic
6.
Trop Med Int Health ; 23(10): 1110-1117, 2018 10.
Article in English | MEDLINE | ID: mdl-30053341

ABSTRACT

OBJECTIVES: To evaluate the antimony (Sb) in plasma of patients who underwent a standardised meglumine antimoniate (MA) intralesional infiltration protocol for cutaneous leishmaniasis treatment. METHODS: The level of Sb in plasma was determined by atomic absorption spectroscopy, before and 1, 2, 4 and 6 hours after the first intralesional infiltration of MA to determine the parameters peak concentrations (C1 h ), area under curve of drug concentration in plasma from zero to 6 h (AUC0-6 h ) and elimination half-life (t½) of Sb. Blood samples were also collected weekly during the treatment period, always before infiltration. RESULTS: Fourteen patients underwent MA intralesional infiltration with doses ranging from 0.8 to 9 mg Sb/kg at the first infiltration. The C1 h ranged from 3850 to 47 095 mg × h/L and was the highest concentration obtained for 11 of 14 patients after the first intralesional infiltration of MA. A rapid initial phase of distribution lasting up to 4 h (2.6 ± 0.34 h) was followed by a slower elimination phase. Total skin lesion area, C1 h and AUC(0-6 h) were related to the dose of Sb infiltered (P < 0.05). Plasma Sb in samples collected weekly before the infiltration revealed antimony concentrations below the quantification limit (15.0 µg Sb/l) during the treatment period. CONCLUSIONS: Sb is quickly absorbed and eliminated after intralesional administration of MA, in a pattern similar to that reported with the Sb systemic administration. Using a therapeutic schedule limited to weekly intralesional infiltration of doses <10 mg Sb/kg does not result in plasma Sb accumulation.


Subject(s)
Antimony/blood , Antiprotozoal Agents/administration & dosage , Leishmaniasis, Cutaneous/drug therapy , Meglumine Antimoniate/administration & dosage , Adult , Female , Humans , Injections, Intralesional , Leishmaniasis, Cutaneous/pathology , Male , Middle Aged , Young Adult
7.
Environ Pollut ; 237: 917-925, 2018 Jun.
Article in English | MEDLINE | ID: mdl-29429611

ABSTRACT

The long-term associations between multiple metals and incident diabetes are uncertain. We aimed to examine the relationship between plasma concentrations of 23 metals and the incidence of type 2 diabetes among Chinese senior adults. We quantified fasting plasma concentrations of 23 metals by inductively coupled plasma mass spectrometry among 1039 incident diabetes cases and 1039 controls (age and sex matched) nested in a prospective study, the Dongfeng-Tongji cohort. Both cases and controls were free of diabetes at baseline (2008-2010), incident diabetes were identified using the following criteria: fasting glucose ≥ 7.0 mmoL/l; or hemoglobin A1c (HbA1c) ≥ 6.5%; or self-reported physician diagnosis of diabetes or use of anti-diabetic medication during the follow-up visits in 2013. In the conditional logistic regression models, the multivariable adjusted ORs (95% CIs) of diabetes across quartiles (Q1-Q4) of metal concentrations were as follows: titanium, 1.00, 0.92, 1.31, 1.38 (1.00-1.91, Ptrend = 0.011); selenium, 1.00, 1.08, 1.45, 1.27 (0.93-1.74, Ptrend = 0.05); and antimony, 1.00, 0.79, 0.77, 0.60 (0.44-0.83, Ptrend = 0.002). Arsenic was significantly associated with diabetes in the crude model (ORs comparing extreme quartiles 1.30; 1.02-1.65; Ptrend = 0.006), but was not significant after adjustment for socio-demographic factors. No significant associations were found for other metals. In conclusion, titanium and selenium were positively while antimony was negatively associated with incident diabetes.


Subject(s)
Environmental Exposure/statistics & numerical data , Environmental Pollutants/blood , Metals/blood , Adult , Aged , Antimony/blood , Arsenic/blood , Asian People , China , Diabetes Mellitus, Type 2/blood , Female , Humans , Incidence , Logistic Models , Male , Middle Aged , Prospective Studies , Titanium/blood
8.
Toxicol Lett ; 288: 136-142, 2018 May 15.
Article in English | MEDLINE | ID: mdl-29462692

ABSTRACT

Antimony is a widely used heavier pnictogens in industry, and its toxicity has been a matter of concern. Although previous studies have suggested that antimony may have the function as either a tumor suppressor or an oncogene in several cancers, the molecular basis underlying antimony-mediated transformation is still unclear. In the current study, we attempt to elucidate the potential role of antimony in the development of prostate cancer. Our results showed that the concentration of antimony was much higher in serum of prostate cancer patients, and was closely associated with poor outcome of patients who underwent radical prostatectomy. Additionally, low dose of antimony could promote proliferation and invasion of androgen-dependent prostate cancer cell line LNCaP cells in vitro and in vivo. The mechanistic studies demonstrated that exposure to antimony triggered the phosphorylation of androgen receptor (AR), which transcriptionally regulates the expression of androgen-related targets, including PSA and NKX3.1. Overall, our results unearthed that antimony could promote tumor growth by mimicking androgen activity in androgen-dependent prostate cancer cells. Therefore, these findings expanded our understanding on the molecular mechanism of antimony in tumorigenesis and tumor progression of prostate cancer, and it appears to be an inspiring strategy to restrain prostate cancer by inhibiting antimony-induced androgen-like effects.


Subject(s)
Androgens/pharmacology , Antimony/pharmacology , Prostatic Neoplasms/pathology , Androgen Antagonists/pharmacology , Animals , Antimony/blood , Cell Line, Tumor , Cell Proliferation/drug effects , Homeodomain Proteins/biosynthesis , Homeodomain Proteins/drug effects , Humans , Male , Mice , Mice, Inbred BALB C , Phosphorylation , Prostate-Specific Antigen/biosynthesis , Prostate-Specific Antigen/drug effects , Prostatectomy , Prostatic Neoplasms/blood , Prostatic Neoplasms/surgery , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , Receptors, Androgen/drug effects , Transcription Factors/biosynthesis , Transcription Factors/drug effects , Treatment Outcome
9.
PLoS One ; 12(12): e0189169, 2017.
Article in English | MEDLINE | ID: mdl-29206878

ABSTRACT

BACKGROUND: The toxic trace elements mercury (Hg), lead (Pb), cadmium (Cd) and antimony (Sb) are transferred over the placenta to the fetus and secreted into the breastmilk. All four elements bioaccumulate in the body and as maternal age at delivery is increasing in industrialized countries, the burden of toxic trace elements in never-pregnant women of fertile age is of concern. METHODS: Healthy, never-pregnant women aged 18 to 40 years (n = 158) were recruited between June 2012 and March 2015 in Bergen, Norway. Clinical data were collected and non-fasting venous blood samples were analyzed for whole blood Hg, Pb and Cd and serum Sb by ICP-MS and related to diet and life style factors. RESULTS: In a multiple linear regression model, increasing age was associated with higher levels of Hg and Sb, but diet and life style factors were more important predictors. Median whole blood Hg was increased by a factor of 70 in women who had fish for dinner ≥1/week, compared to women who rarely or never ate fish (p<0.001). Alcohol intake was the strongest predictor for whole blood Pb, while use of tobacco was the strongest predictor for whole blood Cd. Being a vegetarian was associated with lower levels of both Hg and Sb. CONCLUSIONS: As toxic trace elements tend to bioaccumulate in the body, increasing maternal age at delivery may represent a threat to the next generation. In a group of healthy Norwegian never-pregnant women, age contributed to Hg and Sb levels, but diet and life style factors were stronger determinants of whole blood Hg, Pb, Cd and serum Sb levels. Continuous public actions are needed to reduce modifiable and preventable sources of potentially deleterious toxins to minimize the exposure in children and fertile women.


Subject(s)
Antimony/blood , Cadmium/blood , Lead/blood , Mercury/blood , Adolescent , Adult , Female , Humans , Life Style , Norway , Young Adult
10.
Am J Kidney Dis ; 70(5): 696-704, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28838766

ABSTRACT

BACKGROUND: Low concentrations and excessive concentrations of trace elements have been commonly reported in hemodialysis patients, but available studies have several important limitations. STUDY DESIGN: Random sample of patients drawn from a prospective cohort. SETTING & PARTICIPANTS: 198 incident hemodialysis patients treated in 3 Canadian centers. MEASUREMENTS: We used mass spectrometry to measure plasma concentrations of the 25 elements at baseline, 6 months, 1 year, and 2 years following enrollment in the cohort. We focused on low concentrations of zinc, selenium, and manganese and excessive concentrations of lead, arsenic, and mercury; low and excessive concentrations of the other 19 trace elements were treated as exploratory analyses. Low and excessive concentrations were based on the 5th and 95th percentile plasma concentrations from healthy reference populations. RESULTS: At all 4 occasions, low zinc, selenium, and manganese concentrations were uncommon in study participants (≤5.1%, ≤1.8%, and ≤0.9% for zinc, selenium, and manganese, respectively) and a substantial proportion of participants had concentrations that exceeded the 95th percentile (≥65.2%, ≥74.2%, and ≥19.7%, respectively). Almost all participants had plasma lead concentrations above the 95th percentile at all time points. The proportion of participants with plasma arsenic concentrations exceeding the 95th percentile was relatively constant over time (9.1%-9.8%); the proportion with plasma mercury concentrations that exceeded the 95th percentile varied between 15.2% and 29.3%. Low arsenic, platinum, tungsten, and beryllium concentrations were common (>50%), as were excessive cobalt, manganese, zinc, vanadium, cadmium, selenium, barium, antimony, nickel, molybdenum, lead, and chromium concentrations. CONCLUSIONS: There was no evidence that low zinc, selenium, or manganese concentrations exist in most contemporary Canadian hemodialysis patients. Some patients have excessive plasma arsenic and mercury concentrations, and excessive lead concentrations were common. These findings require further investigation.


Subject(s)
Kidney Failure, Chronic/blood , Trace Elements/blood , Adolescent , Adult , Aged , Antimony/blood , Arsenic/blood , Barium/blood , Beryllium/blood , Cadmium/blood , Chromium/blood , Cobalt/blood , Cohort Studies , Female , Humans , Kidney Failure, Chronic/therapy , Lead/blood , Male , Manganese/blood , Mass Spectrometry , Mercury/blood , Middle Aged , Molybdenum/blood , Nickel/blood , Platinum/blood , Prospective Studies , Renal Dialysis , Selenium/blood , Tungsten/blood , Vanadium/blood , Young Adult , Zinc/blood
11.
Article in English | MEDLINE | ID: mdl-28672853

ABSTRACT

This study investigated antimony exposure among employees in industries in Taiwan and evaluated whether their immunologic markers were associated with antimony exposure. We recruited 91 male workers and 42 male office administrators from 2 glass manufacturing plants, 1 antimony trioxide manufacturing plants, and 2 engineering plastic manufacturing plants. Air samples were collected at worksites and administrative offices, and each participant provided specimens of urine, blood, and hair to assay antimony levels. We also determined white blood cells, lymphocyte, and monocyte, IgA, IgE, and IgG in blood specimens. The mean antimony concentration in the air measured at worksites was much higher in the antimony trioxide plant (2.51 ± 0.57 mg/m³) than in plastic plants (0.21 ± 0.06 mg/m³) and glass plants (0.14 ± 0.01 mg/m³). Antimony levels in blood, urine, and hair measured for participants were correlated with worksites and were higher in workers than in administrators. The mean serum IgG, IgA, and IgE levels were lower in workers than in administrators (p < 0.001). Serum IgA and IgE levels in participants were negatively associated with antimony levels in air samples of workplaces, and in blood, urine, and hairs of participants. Serum IgG and IgE of all participants were also negatively associated with antimony levels in their hairs. In conclusion, the antimony exposure is greater for workers employed in the five industrial plants than for administrators. This study suggests serum IgG, IgA, and IgE levels are negatively associated with antimony exposure.


Subject(s)
Air Pollutants/chemistry , Antimony/blood , Hair/chemistry , Metallurgy , Occupational Exposure/analysis , Adult , Antimony/chemistry , Antimony/urine , Biomarkers , Humans , Male , Taiwan
12.
J Int Soc Sports Nutr ; 14: 19, 2017.
Article in English | MEDLINE | ID: mdl-28615997

ABSTRACT

BACKGROUND: The aim of this study was to observe the concentrations of trace metals boron, lithium, rubidium, antimony, tin and strontium in the serum of athletes from different modalities and sedentary subjects and the possible influence that different energy sports training modalities can have on their concentration. METHODS: Eighty professional athletes and 31 sedentary males participated in the present survey. All of them were living in Cáceres (Spain). Serum boron, lithium, rubidium, antimony, tin and strontium analysis was performed by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). RESULTS: The results show higher concentrations in athletes on tin (p < 0.01), rubidium and antimony (p < 0.001) than the control group. In the case of tin, this item had the highest concentrations only in aerobic sports modalities. Regarding rubidium and antimony, the highest concentrations are found in athletes with lower oxygen consumption (aerobic-anaerobic) (p < 0.001), followed by anaerobic group (p < 0.001). CONCLUSION: Our research shows that, probably due to increased water and air intake, especially, trace elements rubidium, antimony and tin reveal major differences in serum concentration of athletes in relation to sedentary subjects. On the other hand, physical training does not change the serum concentration of Boron, Lithium and strontium.


Subject(s)
Exercise , Trace Elements/blood , Adolescent , Adult , Anthropometry , Antimony/blood , Athletes , Boron/blood , Case-Control Studies , Humans , Lithium/blood , Male , Rubidium/blood , Spain , Strontium/blood , Tin/blood , Young Adult
13.
Environ Res ; 156: 247-252, 2017 07.
Article in English | MEDLINE | ID: mdl-28363141

ABSTRACT

BACKGROUND: Antimony is used as a flame-retardant in textiles and plastics, in semiconductors, pewter, and as pigments in paints, lacquers, glass and pottery. Subacute or chronic antimony poisoning has been reported to cause sleeplessness. The prevalence of short sleep duration (<7h/night) has been reported to be 37.1% in the general US population, and obstructive sleep apnea (OSA) affects 12-28 million US adults. Insufficient sleep and OSA have been linked to the development of several chronic conditions including diabetes, cardiovascular disease, obesity and depression, conditions that pose serious public health threats. OBJECTIVE: To investigate whether there is an association between antimony exposure and sleep-related disorders in the US adult population using the National Health and Nutrition Examination Survey (NHANES) 2005-2008. METHODS: We performed multivariate logistic regression to analyze the association of urinary antimony with several sleep disorders, including insufficient sleep and OSA, in adult (ages 20 years and older) participants of NHANES 2005-2008 (n=2654). RESULT: We found that participants with higher urinary antimony levels had higher odds to experience insufficient sleep (≤6h/night) (OR 1.73; 95%CI; 1.04, 2.91) as well as higher odds to have increased sleep onset latency (>30min/night). Furthermore, we found that higher urinary antimony levels in participants were associated with OSA (OR 1.57; 95%CI; 1.05, 2.34), sleep problems, and day-time sleepiness. CONCLUSION: In this study, we found that urinary antimony was associated with higher odds to have insufficient sleep and OSA. Because of the public health implications of sleep disorders, further studies, especially a prospective cohort study, are warranted to evaluate the association between antimony exposure and sleep-related disorders.


Subject(s)
Antimony/metabolism , Antimony/toxicity , Sleep Wake Disorders/chemically induced , Sleep Wake Disorders/epidemiology , Adult , Aged , Aged, 80 and over , Antimony/blood , Antimony/urine , Environmental Pollutants/blood , Environmental Pollutants/metabolism , Environmental Pollutants/toxicity , Environmental Pollutants/urine , Female , Humans , Male , Middle Aged , Nutrition Surveys , Prevalence , United States/epidemiology , Young Adult
14.
Int J Nanomedicine ; 11: 2305-18, 2016.
Article in English | MEDLINE | ID: mdl-27307731

ABSTRACT

There is a great need for orally active drugs for the treatment of the neglected tropical disease leishmaniasis. Amphiphilic Sb(V) complexes, such as 1:3 Sb-N-octanoyl-N-methylglucamide complex (SbL8), are promising drug candidates. It has been previously reported that SbL8 forms kinetically stabilized nanoassemblies in water and that this simple dispersion exhibits antileishmanial activity when given by oral route to a murine model of visceral leishmaniasis. The main objective of the present work was to interfere in the structural organization of these nanoassemblies so as to investigate their influence on the oral bioavailability of Sb, and ultimately, optimize an oral formulation of SbL8 for the treatment of cutaneous leishmaniasis. The structural organization of SbL8 nanoassemblies was manipulated through addition of propylene glycol (PG) to the aqueous dispersion of SbL8. The presence of 50% (v/v) PG resulted in the loss of hydrophobic microenvironment, as evidenced by fluorescence probing. However, nanostructures were still present, as demonstrated by dynamic light scattering, small-angle X-ray scattering, and atomic force microscopy (AFM). A remarkable property of these nanoassemblies, as revealed by AFM analysis, is the flexibility of their supramolecular organization, which showed changes as a function of the solvent and substrate polarities. The formulation of SbL8 in 1:1 water:PG given orally to mice promoted significantly higher and more sustained serum levels of Sb, when compared to SbL8 in water. The new formulation, when given as repeated doses (200 mg Sb/kg/day) to BALB/c mice infected with Leishmania amazonensis, was significantly more effective in reducing the lesion parasite burden, compared to SbL8 in water, and even, the conventional drug Glucantime(®) given intraperitoneally at the same dose. In conclusion, this work introduces a new concept of polarity-sensitive nanocarrier that was successfully applied to optimize an oral formulation of Sb(V) for treating cutaneous leishmaniasis.


Subject(s)
Antimony/therapeutic use , Antiprotozoal Agents/therapeutic use , Drug Carriers/chemistry , Leishmaniasis, Cutaneous/drug therapy , Nanoparticles/chemistry , Administration, Oral , Animals , Antimony/blood , Antimony/pharmacokinetics , Antiprotozoal Agents/chemistry , Antiprotozoal Agents/pharmacokinetics , Disease Models, Animal , Female , Hydrophobic and Hydrophilic Interactions , Meglumine/therapeutic use , Meglumine Antimoniate , Mice, Inbred BALB C , Microscopy, Atomic Force , Nanoparticles/ultrastructure , Organometallic Compounds/therapeutic use , Scattering, Small Angle , Solvents , Treatment Outcome , X-Ray Diffraction
15.
Anal Biochem ; 492: 1-7, 2016 Jan 01.
Article in English | MEDLINE | ID: mdl-26278170

ABSTRACT

This work presents a cloud-point extraction process using the micelle-mediated extraction method for simultaneous preconcentration and determination of Sb(III) and Sb(V) species in biological and environmental samples as a prior preconcentration step to their spectrophotometric determination. The analytical system is based on the selective reaction between Sb(III) and 3-dichloro-6-(3-carboxy-2-hydroxy-1-naphthylazo)quinoxaline (DCHNAQ) in the presence of cetyltrimethylammonium bromide (CTAB) and potassium iodide at pH 4.5. Total Sb concentration was determined after reduction of Sb(V) to Sb(III) in the presence of potassium iodide and ascorbic acid. The optimal reaction conditions and extraction were studied, and the analytical characteristics of the method (e.g., limits of detection and quantification, linear range, preconcentration, improvement factors) were obtained. Linearity for Sb(III) was obeyed in the range of 0.2-20 ng ml(-1). The detection and quantification limits for the determination of Sb(III) were 0.055 and 0.185 ng ml(-1), respectively. The method has a lower detection limit and wider linear range, inexpensive instrument, and low cost, and is more sensitive compared with most other methods. The interference effect of some anions and cations was also studied. The method was applied to the determination of Sb(III) in the presence of Sb(V) and total antimony in blood plasma, urine, biological, and water samples.


Subject(s)
Antimony/analysis , Chemistry Techniques, Analytical/methods , Spectrophotometry , Animals , Antimony/blood , Antimony/urine , Cetrimonium , Cetrimonium Compounds/chemistry , Feces/chemistry , Femur/chemistry , Fresh Water/analysis , Hair/chemistry , Humans , Ions/chemistry , Kidney/chemistry , Limit of Detection , Potassium Iodide/chemistry , Rats
16.
Int J Environ Health Res ; 26(2): 158-74, 2016.
Article in English | MEDLINE | ID: mdl-26179629

ABSTRACT

This study assessed lead, arsenic, and antimony in maternal and cord blood, and associations between maternal concentrations and social determinants in the Bolivian mining city of Oruro using the baseline assessment of the ToxBol/Mine-Niño birth cohort. We recruited 467 pregnant women, collecting venous blood and sociodemographic information as well as placental cord blood at birth. Metallic/semimetallic trace elements were measured using inductively coupled plasma mass spectrometry. Lead medians in maternal and cord blood were significantly correlated (Spearman coefficient = 0.59; p < 0.001; 19.35 and 13.50 µg/L, respectively). Arsenic concentrations were above detection limit (3.30 µg/L) in 17.9% of maternal and 34.6% of cord blood samples. They were not associated (Fischer's p = 0.72). Antimony medians in maternal and cord blood were weakly correlated (Spearman coefficient = 0.15; p < 0.03; 9.00 and 8.62 µg/L, respectively). Higher concentrations of toxic elements in maternal blood were associated with maternal smoking, low educational level, and partner involved in mining.


Subject(s)
Antimony/blood , Arsenic/blood , Environmental Pollutants/blood , Fetal Blood/chemistry , Lead/blood , Maternal Exposure , Adolescent , Adult , Bolivia , Environmental Monitoring , Female , Humans , Mass Spectrometry , Mining , Socioeconomic Factors , Urban Population , Young Adult
17.
Environ Sci Pollut Res Int ; 23(1): 198-205, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26517997

ABSTRACT

This study was aimed to examine the prevalence of food insecurity and what social, health, and environmental characteristics could constitute such situation in a national and population-based setting. Data was retrieved from the National Health and Nutrition Examination Survey, 2005-2006. Information on demographics, lifestyle factors, self-reported ever medical conditions in the past and self-reported food security conditions in the last 12 months calculated on the household level was obtained by household interview. Bloods and urines (subsample) were collected at the interview as well. Only adults aged 20 years and above (n = 4979) were included for statistical analysis in the present study. Chi-square test, t test, and survey-weighted logistic regression modeling were performed. Three thousand eight hundred thirty-four (77.9%) people were with full food security, 466 (9.5%) people were with marginal food security and 624 (12.7%) people were with low or very low food security. Being younger, having higher ratios of family income to poverty thresholds (due to low level of education or lack of financial support), having prior asthma, arthritis, chronic bronchitis, depression, diabetes, eczema, emphysema or liver problems, having higher levels of serum cotinine, urinary antimony, bisphenol A, pesticides, or having lower levels of urinary Benzophenone-3 were associated with food insecurity. In addition to socioeconomic and smoking conditions, evidence on people with several prior health conditions and being exposed to environmental chemicals and food insecurity is further provided. Future social, health and environmental policy, and programs protecting people from food insecurity by considering both health and environmental factors mentioned above would be suggested.


Subject(s)
Food Supply/standards , Liver Diseases/urine , Mental Disorders/urine , Pesticides/urine , Adolescent , Adult , Aged , Aged, 80 and over , Antimony/blood , Antimony/urine , Asthma/blood , Asthma/urine , Benzhydryl Compounds/blood , Benzhydryl Compounds/urine , Benzophenones/blood , Benzophenones/urine , Diabetes Mellitus/blood , Diabetes Mellitus/urine , Female , Food Supply/statistics & numerical data , Humans , Liver Diseases/blood , Logistic Models , Male , Mental Disorders/blood , Middle Aged , Nutrition Surveys , Pesticides/blood , Phenols/blood , Phenols/urine , Poverty , Self Report , Young Adult
18.
PLoS One ; 10(1): e0114796, 2015.
Article in English | MEDLINE | ID: mdl-25615452

ABSTRACT

We assessed the reactivity of Sb(V) in human blood. Sb(V) reactivity was determined using an HPLC-HG-AFS hyphenated system. Sb(V) was partially reduced to Sb(III) in blood incubation experiments; however, Sb(III) was a highly unstable species. The addition of 0.1 mol L(-1) EDTA prevented Sb(III) oxidation, thus enabling the detection of the reduction of Sb(V) to Sb(III). The transformation of Sb(V) to Sb(III) in human whole blood was assessed because the reduction of Sb(V) in human blood may likely generate redox side effects. Our results indicate that glutathione was the reducing agent in this reaction and that Sb(V) significantly decreased the GSH/GSSG ratio from 0.32 ± 0.09 to 0.07 ± 0.03. Moreover, the presence of 200 ng mL(-1) of Sb(V) increased the activity of superoxide dismutase from 4.4 ± 0.1 to 7.0 ± 0.4 U mL(-1) and decreased the activity of glutathione peroxidase from 62 ± 1 to 34 ± 2 nmol min(-1) mL(-1).


Subject(s)
Antimony/blood , Adult , Female , Glutathione Disulfide/blood , Humans , Male , Oxidation-Reduction
19.
Clin Biochem ; 48(3): 135-9, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25448028

ABSTRACT

OBJECTIVES: We developed and validated a simplified sample preparation for the analysis of antimony (Sb), bismuth (Bi), manganese (Mn), and zinc (Zn) in whole blood. This simplification included a reduction in sample volume, removal of a lengthy acidic digestion, and optimization of the internal standard. DESIGN AND METHODS: Measurement of Sb, Bi, Mn and Zn in whole blood was conducted using inductively coupled-plasma mass spectrometry. Method performance characteristics, including intra- and inter-assay imprecision, accuracy, linearity, AMR, sensitivity, carryover, sample stability and assay stability were determined in accordance with clinical laboratory standards. In addition, analytical and clinical recoveries were assessed to investigate comparability between goat blood matrix and pooled patient blood. RESULTS: Established assay performance characteristics included inter- and intra-assay imprecision <4.5% and carryover of <0.04% for all four elements, analytical measurement range of 1 to 25 µg/L (Sb and Bi), 1 to 80 µg/L (Mn), and 50 to 1500 µg/dL (Zn), limit of quantification of 1 µg/L (Sb, Bi, Mn) and 50 µg/dL (Zn) (coefficient of variation <14%), proportional bias of 0.96 and constant bias of -0.28 (Sb), 0.94 and -0.45 (Bi), 1.07 and -0.37 (Mn) and 0.96 and +18.05 (Zn) based upon repeat patient samples, proficiency testing samples, and comparison to an outside reference laboratory. CONCLUSION: This method overcomes the laborious acidic heat digestion previously used and replaces it with a simplified sample preparation involving an alkaline dilution. The method requires minimal sample preparation with the dilution of alkaline diluent and is validated to quantify Sb and Bi from 1 to 25 µg/L, Mn from 1 to 80 µg/L, and Zn from 50 to 1500 µg/dL in whole blood.


Subject(s)
Analytic Sample Preparation Methods/methods , Metals, Heavy/blood , Spectrophotometry, Atomic/methods , Analytic Sample Preparation Methods/economics , Animals , Antimony/blood , Bismuth/blood , Goats , Humans , Manganese/blood , Reproducibility of Results , Zinc/blood
20.
Cancer Causes Control ; 23(7): 1065-74, 2012 Jul.
Article in English | MEDLINE | ID: mdl-22576580

ABSTRACT

PURPOSE: Few studies have evaluated the role of micronutrients or trace elements in breast cancer development among BRCA1 mutation carriers. To investigate a possible role of dietary and environmental exposures on cancer risk, we undertook an exploratory study, using a matched case-control design (n = 48 cases and 96 controls), to evaluate the relationships between plasma levels of 14 micronutrients and breast cancer risk among BRCA1 mutation carriers in Poland. METHODS: We estimated the univariate odds ratios (OR) and 95 % confidence intervals (CI) for breast cancer associated with plasma levels for each of 14 micronutrients. RESULTS: Of the 14 analytes quantified, significant differences between cases and controls were seen for two (iron and retinol; p = 0.009 and p = 0.03, respectively). Women in the highest tertile of plasma iron had a 57 % lower risk, compared with those in the lowest quartile (OR = 0.43; 95 % CI 0.18-1.04; p for trend = 0.06). Increasing antimony levels were associated with an increased risk of breast cancer (p for trend = 0.05). Women in the highest tertile had a 2.43-fold increase in breast cancer risk compared with women in the lowest tertile (OR = 2.43; 95 % CI 1.00-5.91). CONCLUSIONS: This study provides some preliminary evidence regarding a role of diet, specifically iron and antimony, in the etiology of BRCA1-associated breast cancer. Prospective studies are necessary to confirm these findings.


Subject(s)
BRCA1 Protein/genetics , Breast Neoplasms/blood , Breast Neoplasms/genetics , Micronutrients/blood , Mutation , Trace Elements/blood , Adult , Aged , Analysis of Variance , Antimony/blood , Case-Control Studies , Female , Heterozygote , Humans , Iron/blood , Logistic Models , Middle Aged , Odds Ratio , Prospective Studies , Risk Assessment , Risk Factors , Young Adult
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