Assessment of the Relationship Between Liver Enzymes and Cardiovascular Disease: A Study in Bangladeshi Adults.

OBJECTIVES: Elevated liver enzyme levels are suggested to be associated with an increased risk of cardiovascular disease (CVD). However, few studies have explored the relationship between liver enzymes and myocardial infarction (MI). This study aimed to evaluate the potential association of elevated liver enzymes with MI within a population group in Bangladesh. METHODS: In this cross-sectional study, 348 participants were enrolled, 189 with MI in the CVD group and 159 in the control group. Serum levels of liver enzymes (AST, ALT and GGT) and other biochemical parameters were measured using standard methods. Multivariate logistic regression models were applied to determine the associations between elevated liver enzymes and CVD. RESULT: In the CVD group, 51.6%, 30.9% and 67.7% of individuals had elevated serum AST, ALT and GGT levels, respectively. On the contrary, the control group had 17.0%, 15.1% and 35.2% of individuals with high serum AST, ALT and GGT levels, respectively. Overall, 71.8% of the subjects in the CVD group and 44.7% of the subjects in the control group had at least one or more elevated liver enzymes (p < 0.001). The mean level of all three liver enzymes was significantly higher in the CVD group than in the control group (p < 0.001). In both the CVD and control groups, males had higher levels of liver enzymes than females. In the regression models, the serum levels of AST, ALT and GGT showed a positive and independent association with the prevalence of CVD (p < 0.001). However, GGT showed the strongest association among the three enzymes. CONCLUSIONS: This study shows a high prevalence of liver enzyme abnormalities in individuals with CVD. Serum levels of AST, ALT and GGT were independently associated with the prevalence of CVD. This suggests that measuring liver enzyme levels could be a useful marker in predicting CVD at an early stage.

Association of serum xanthine oxidase levels with hypertension: a study on Bangladeshi adults.

Xanthine oxidase (XO) is a metalloflavoenzyme associated with the uric acid formation in purine metabolism. Serum XO has been suggested to be associated with liver and kidney dysfunction, diabetes and cardiovascular diseases. However, there is limited information on the relationship between serum XO levels and hypertension. This study aimed to assess the relationship between serum XO levels and hypertension in Bangladeshi adults. In this study, fasting blood samples were collected from 312 participants (225 males and 87 females), aged ≥ 20 years. Serum levels of XO were determined by ELISA and other biochemical parameters including serum uric acid (SUA) were measured by colorimetric methods. Hypertension was defined as SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg or self-reported recent use of anti-hypertensive medications. Association between serum XO levels and hypertension was evaluated by multinomial logistic regression analysis. The mean level of XO was significantly higher (p < 0.001) in females (5.8 ± 3.2 U/L) than in males (3.9 ± 2.5 U/L). When the participants were divided by blood pressure levels, the mean level of serum XO was significantly higher (p < 0.01) in the hypertensive group (5.0 ± 2.7 U/L) compared to the normotensive control group (4.0 ± 2.7 U/L). An increasing trend for SBP and DBP levels was observed across the XO quartiles (at least p < 0.01 for both cases). A significant positive correlation was found for XO with SBP and DBP (p < 0.01). In regression analysis, the serum levels of XO showed a significant and independent association with hypertension prevalence. In conclusion, the mean level of serum XO was significantly higher in hypertensive individuals and XO was independently associated with the prevalence of hypertension. Our results indicate that XO may have a potential role in the pathophysiology of elevated blood pressure through generating of reactive oxygen species. Further large-scale longitudinal studies are needed to determine the underlying mechanisms between XO and hypertension.

Incidence and Risk of Lung Cancer in Tuberculosis Patients, and Vice Versa: A Literature Review of the Last Decade.

Background: The incidence and risk of both lung cancer (LC) and tuberculosis (TB) are increasing rapidly. These two diseases frequently exist together and can influence the incidence and risk of each other. The aim of the current review was to summarize the incidence and risk of LC in TB patients, and vice versa, short out research gap, and contemplate future research perspectives. Methodology. PubMed and Scopus databases, and Google Scholar search engine were searched for epidemiological studies that investigated the incidence and risk of TB and LC, published since January 2011 to April 2022, and written in English. We used the searching keyword "tuberculosis" combined with "lung cancer" and associated medical subject heading (MeSH) to retrieve eligible research articles. We retrieved information's regarding the diagnosis of TB and LC, confounders, the associations of TB and LC, and incidence and risks of each other. Results: We found higher incidence rate and risks (1.64 to 6 times higher) of LC in TB patients in comparison to non-TB participants. However, the incidence rate and risks of TB in LC patients were comparatively low. Male patients were exhibited higher risks than female. The medical comorbidities, smoking habits, and age can also influence the associations and risks of LC in TB patients or vice versa. Conclusion: Our summarized studies might suggest that existing active TB may increase the incidence and risk of LC. However, large prospective cohort study is warranted to explore the real scenario worldwide.

Prevalence and risk factors of general and abdominal obesity and hypertension in rural and urban residents in Bangladesh: a cross-sectional study.

BACKGROUND: Obesity and hypertension are global health concerns. Both are linked with increased risks of all-cause and cardiovascular mortality. Several early studies reported the prevalence of obesity and hypertension in Bangladeshi adults, but the associated factors in this country population are not clear yet. We aimed to estimate the prevalence and related risk factors of general and abdominal obesity and hypertension in rural and urban adults in Bangladesh. METHODS: In this cross-sectional study, data (n = 1410) was collected on rural (n = 626) and urban (n = 784) adults from eight divisional regions of Bangladesh. Both anthropometric and socio-demographic measurements were recorded in a standardized questionnaire form. General and abdominal obesity were defined based on WHO proposed cut-off values and hypertension was defined by SBP ≥ 140 mmHg and/or, DBP ≥ 90 mmHg and/or, intake of anti-hypertensive drugs at the time of data collection. Multivariable logistic regression analyses were performed to assess the relationship of general and abdominal obesity and hypertension with various factors. RESULTS: The overall prevalence of general obesity, abdominal obesity and hypertension was 18.2, 41.9 and 30.9%, respectively. The women had a higher prevalence of general obesity (25.2%), abdominal obesity (56.1%) and hypertension (32.3%) compared to the men (12.2, 29.0, and 29.7%, respectively). The prevalence of both general and abdominal obesity was higher in urban participants (21.7 and 46.6%, respectively) than in the rural participants (13.8 and 35.1%, respectively), whereas, the rural participants had a higher prevalence of hypertension (35.1%) compared to the urban participants (27.5%). In geographical region comparison, the prevalence of general and abdominal obesity and hypertension were higher in participants enrolled from Dhaka (30.8%), Khulna (63.6%) and Mymensingh (43.5%) regions, respectively compared to other regions. In regression analysis, increased age, place of residence and less physical activity were positively associated with the increased risk of both types of obesity and hypertension. The analysis also showed a significant positive association between high BMI and an increased risk of hypertension. CONCLUSION: This study shows a high prevalence of obesity and hypertension in rural and urban adults. Increased age, inadequate physical activity and place of residence were significant determinants of general and abdominal obesity and hypertension. A comprehensive intervention program focusing on modifiable risk factors such as lifestyles and food habits is needed to increase awareness and prevent the burden of obesity and hypertension in the Bangladeshi population.

Life-Time Environmental Chemical Exposure and Obesity: Review of Epidemiological Studies Using Human Biomonitoring Methods.

The exponential global increase in the incidence of obesity may be partly attributable to environmental chemical (EC) exposure. Humans are constantly exposed to ECs, primarily through environmental components. This review compiled human epidemiological study findings of associations between blood and/or urinary exposure levels of ECs and anthropometric overweight and obesity indices. The findings reveal research gaps that should be addressed. We searched MEDLINE (PubMed) for full text English articles published in 2006-2020 using the keywords "environmental exposure" and "obesity". A total of 821 articles were retrieved; 102 reported relationships between environmental exposure and obesity indices. ECs were the predominantly studied environmental exposure compounds. The ECs were grouped into phenols, phthalates, and persistent organic pollutants (POPs) to evaluate obesogenic roles. In total, 106 articles meeting the inclusion criteria were summarized after an additional search by each group of EC combined with obesity in the PubMed and Scopus databases. Dose-dependent positive associations between bisphenol A (BPA) and various obesity indices were revealed. Both individual and summed di(2-ethylhexyl) phthalate (DEHP) and non-DEHP metabolites showed inconsistent associations with overweight and obesity indices, although mono-butyl phthalate (MBP), mono-ethyl phthalate (MEP), and mono-benzyl phthalate (MBzP) seem to have obesogenic roles in adolescents, adults, and the elderly. Maternal exposure levels of individual POP metabolites or congeners showed inconsistent associations, whereas dichlorodiphenyldichloroethylene (DDE) and perfluorooctanoic acid (PFOA) were positively associated with obesity indices. There was insufficient evidence of associations between early childhood EC exposure and the subsequent development of overweight and obesity in late childhood. Overall, human evidence explicitly reveals the consistent obesogenic roles of BPA, DDE, and PFOA, but inconsistent roles of phthalate metabolites and other POPs. Further prospective studies may yield deeper insights into the overall scenario.

The Presence of Aflatoxin M1 in Milk and Milk Products in Bangladesh.

As milk provides both micro- and macronutrients, it is an important component in the diet. However, the presence of aflatoxin B1 (AFB1) in the feed of dairy cattle results in contamination of milk and dairy products with aflatoxin M1 (AFM1), a toxic metabolite of the carcinogenic mycotoxin. With the aim to determine AFM1 concentrations in milk and milk products consumed in Bangladesh, in total, 145 samples were collected in four divisional regions (Sylhet, Dhaka, Chittagong, and Rajshahi). The samples comprised these categories: raw milk (n = 105), pasteurized milk (n = 15), ultra-high temperature (UHT)-treated milk (n = 15), fermented milk products such as yogurt (n = 5), and milk powder (n = 5). AFM1 levels in these samples were determined through competitive enzyme-linked immunosorbent assay (ELISA). Overall, AFM1 was present in 78.6% of milk and milk products in the range of 5.0 to 198.7 ng/L. AFM1 was detected in 71.4% of raw milk (mean 41.1, range 5.0-198.7 ng/L), and in all pasteurized milk (mean 106, range 17.2-187.7 ng/L) and UHT milk (mean 73, range 12.2-146.9 ng/L) samples. Lower AFM1 levels were found in yogurt (mean 16.9, range 8.3-41.1 ng/L) and milk powder samples (mean 6.6, range 5.9-7.0 ng/L). About one-third of the raw, pasteurized, and UHT milk samples exceeded the EU regulatory limit (50 ng/L) for AFM1 in milk, while AFM1 levels in yogurt and milk powder samples were well below this limit. Regarding regions, lower AFM1 contamination was observed in Chittagong (mean 6.6, max 10.6 ng/L), compared to Sylhet (mean 53.7, max 198.7 ng/L), Dhaka (mean 37.8, max 97.2 ng/L), and Rajshahi (mean 34.8, max 131.4 ng/L). Yet, no significant difference was observed in AFM1 levels between summer and winter season. In conclusion, the observed frequency and levels of aflatoxin contamination raise concern and must encourage further monitoring of AFM1 in milk and milk products in Bangladesh.

Development of a strategic approach for comprehensive detection of organophosphate pesticide metabolites in urine: Extrapolation of cadusafos and prothiofos metabolomics data of mice to humans.

OBJECTIVES: The comprehensive detection of environmental chemicals in biospecimens, an indispensable task in exposome research, is advancing. This study aimed to develop an exposomic approach to identify urinary metabolites of organophosphate (OP) pesticides, specifically cadusafos and prothiofos metabolites, as an example chemical group, using an original metabolome dataset generated from animal experiments. METHODS: Urine samples from 73 university students were analyzed using liquid chromatography-high-resolution mass spectrometry. The metabolome data, including the exact masses, retention time (tR ), and tandem mass spectra obtained from the human samples, were compared with the existing reference databases and with our original metabolome dataset for cadusafos and prothiofos, which was produced from mice to whom two doses of these OPs were orally administered. RESULTS: Using the existing databases, one chromatographic peak was annotated as 2,4-dichlorophenol, which could be a prothiofos metabolite. Using our original dataset, one peak was annotated as a putative cadusafos metabolite and three peaks as putative prothiofos metabolites. Of these, all three peaks suggestive of prothiofos metabolites, 2,4-dichlorophenol, 3,4,5-trihydroxy-6-(2,4-dichlorophenoxy) oxane-2-carboxylic acid, and (2,4-dichlorophenyl) hydrogen sulfate were confirmed as authentic compounds by comparing their peak data with both the original dataset and peak data of the standard reagents. The putative cadusafos metabolite was identified as a level C compound (metabolite candidate with limited plausibility). CONCLUSIONS: Our developed method successfully identified prothiofos metabolites that are usually not a target of biomonitoring studies. Our approach is extensively applicable to various environmental contaminants beyond OP pesticides.

The relationship between serum uric acid and lipid profile in Bangladeshi adults.

BACKGROUND: Although the link between elevated uric acid and metabolic syndrome has been reported in some studies; the relationship of serum uric acid (SUA) with lipid profile has not well studied or little is known so far. This study was conducted to assess the relationship between SUA and lipid profile among the general adults in Bangladesh. METHODS: In total, 280 blood samples were collected from general adult participants (male, n = 150 and female, n = 130) and analyzed for serum lipid profile (TC, TG, HDL and LDL) and SUA levels. The study subjects were divided by quartiles based on SUA levels (Q1: ≤225 µmol/L, Q2: 226-285 µmol/L, Q3: 286-340 µmol/L and Q4: > 340 µmol/L). Linear regression modeling was used to evaluate the relationship between SUA and lipid levels. RESULTS: The prevalence of hyperuricemia was 9.2% in males and 10.4% in females. The mean level of SUA was significantly higher in male (317 ± 90 µmol/L) than in the female (255 ± 65 µmol/L) subjects (p < 0.001). An increasing trend for elevated lipid profile was observed in both gender with increasing levels of SUA in the quartiles (p < 0.05). In regression analysis, a significant positive correlation was found between SUA and TG, TC and LDL (p < 0.01) while an inverse correlation was observed between SUA and HDL (p < 0.01). After adjusting for potential confounders, lipid profile was linearly associated with SUA levels (p < 0.01 for trend). CONCLUSIONS: Present study showed a significant positive relationship for SUA with TG, TC and LDL levels, and an inverse relationship for SUA with HDL. Early prevention of hyperuricemia and dyslipidemia may be helpful to reduce the incidence of associated cardiovascular diseases.

Prevalence of hyperuricemia and the relationship between serum uric acid and obesity: A study on Bangladeshi adults.

BACKGROUND AND OBJECTIVES: Recent studies have shown that hyperuricemia is commonly associated with dyslipidemia, cardiovascular diseases, hypertension and metabolic syndrome. Elevated serum uric acid has been demonstrated to be associated with obesity in the adult population in many countries; however, there is still a lack of evidence for the Bangladeshi population. The aims of this study were to evaluate the prevalence of hyperuricemia and determine the relationship between serum uric acid (SUA) and obesity among the Bangladeshi adults. METHODS: In this cross-sectional study, blood samples were collected from 260 adults (142 males and 118 females) and analyzed for SUA and lipid profile. All participants were categorized as underweight (n = 11), normal (n = 66), overweight (n = 120) and obese (n = 63) according to the body mass index (BMI) scale for the Asian population. Based on SUA concentration the participants were stratified into four quartiles (Q1: < 232 µmol/L, Q2: 232-291 µmol/L, Q3: 292-345 µmol/L and Q4: > 345 µmol/L). RESULTS: The mean age and BMI of the participants were 32.5 ± 13.3 years and 24.9 ± 3.8 kg/m2, respectively. The average level of SUA was 294 ± 90 µmol/L with a significant difference between males and females (p < 0.001). Overall, the estimated prevalence of hyperuricemia was 9.3% with 8.4% in male and 10.2% in female participants. There were significant increases in the prevalence of obesity (17.4%, 22.2%, 28.6% and 31.8%, respectively, p < 0.01 for trend) across the SUA quartiles. A multiple logistic regression analysis revealed that SUA quartiles were independently associated with the presence of obesity (p < 0.01). CONCLUSION: Present study indicates a significant positive relationship between SUA and obesity among the Bangladeshi adults. Therefore, routine measurement of SUA is recommended in obese individuals to prevent hyperuricemia and its related complications.

Association between arsenic exposure and soluble thrombomodulin: A cross sectional study in Bangladesh.

Chronic exposure to arsenic is associated with increased morbidity and mortality from cardiovascular disease (CVD); however, plausible biomarker for early prediction and the underlying mechanism of arsenic-related CVD have not yet been clearly understood. Endothelial dysfunction plays a central role in the development of CVD. We hypothesized that endothelial damage or dysfunction is an important aspect and may be an early event of arsenic-related CVD. Soluble thrombomodulin (sTM) in serum is thought to be a specific and stable marker for endothelial damage or dysfunction. This study was designed to evaluate the association between chronic exposure to arsenic and sTM among human subjects in arsenic-endemic and non-endemic rural areas in Bangladesh. A total of 321 study subjects (217 from arsenic-endemic areas and 104 from a non-endemic area) were recruited. Subjects' arsenic exposure levels (i.e., drinking water, hair and nail arsenic concentrations) were measured by Inductively Coupled Plasma Mass Spectroscopy. The subjects' serum sTM levels were quantified by immunoassay kit. The average sTM levels of the subjects in arsenic-endemic and non-endemic areas were 4.58 ± 2.20 and 2.84 ± 1.29 (ng mL-1) respectively, and the difference was significant (p<0.001). Arsenic exposure levels showed a significant (water arsenic: rs = 0.339, p<0.001, hair arsenic: rs = 0.352, p<0.001 and nail arsenic: rs = 0.308, p<0.001) positive associations with sTM levels. Soluble TM levels were higher in the higher exposure gradients if we stratified the subjects into tertile groups (low, medium and high) based on the arsenic concentrations of the subjects' drinking water, hair and nails. Finally, increased levels of sTM were negatively correlated with high density lipoprotein cholesterol (HDL-C), and positively correlated with intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). Results of this study show that chronic exposure to arsenic has mild to moderate association with sTM levels.

Individual and Combined Effects of Arsenic and Lead on Behavioral and Biochemical Changes in Mice.

Arsenic (As) toxicity has caused an environmental tragedy affecting millions of people in the world. Little is known about the toxic effects of As on neurobehavioral and biochemical changes in vivo. Along this line of metal toxicity, co-exposure of lead (Pb) could aggravate the situation in the host. The present study was designed to explore the combined effects of As and Pb on behavioral changes like anxiety, spatial memory and learning impairment, and blood indices related to organ dysfunction. Exposure of mice to As (10 mg/kg body weight), Pb (10 mg/kg body weight), and As + Pb via drinking water significantly decreased the time spent exploring the open arms while it increased the time spent in the closed arms compared to control mice in the elevated plus maze. The mean latency time of the control group to find the platform decreased significantly during the learning for 7 days compared to all three treated groups in the Morris water maze test, and the As-exposed group spent significantly less time in the desired quadrant as compared to the control group in the probe trial. Both metals posed an anxiety-like behavior and deficits in spatial memory and learning, and also altered blood indices related to liver and kidney dysfunction, and a combined exposure of these metals inhibited the individual accumulation of As and Pb. Taken together, these data suggest that As has more toxic effects on neurobehavioral and biochemical changes than Pb, and there may be antagonism in the effects and accumulation between these two toxicants.

Occurrence of aflatoxin M1 in urines from rural and urban adult cohorts in Bangladesh.

Aflatoxins are important mycotoxins produced by Aspergillus flavus and A. parasiticus, moulds which contaminate mainly grains and nuts, especially in hot and humid climate. Presence of aflatoxin B1 (AFB1), the most toxic one and a potent hepatocarcinogen, has been reported in food and feed in Bangladesh and raised concerns about mycotoxin exposure in the population. Biomonitoring provides the best approach to assess human exposure from various sources and by all routes. Part of the ingested AFB1 is converted in the body to aflatoxin M1 (AFM1), a metabolite that has served as biomarker of AFB1 exposure, as it is excreted in urine, and thus enables non-invasive sampling, a relevant aspect in field studies. This investigation measured the AFM1 concentration in urines collected from adult residents of a rural (n = 52) and an urban (n = 43) area in the Rajshahi district of Bangladesh. The urinary levels of AFM1 were determined by enzyme-linked immunosorbent assay. AFM1 was detected in 46 % of all urine samples at a range of 31-348 pg/mL. The median and mean concentration of AFM1 in urine was 61 and 80 ± 60 pg/mL, respectively. A significant difference (p < 0.05) was found at the mean level of AFM1 between the rural (99 ± 71 pg/mL) and urban (54 ± 15 pg/mL) cohort. Urinary AFM1 levels did not show significant correlations with food frequency data or age, gender and body mass index of the participants. Among them, the highest mean AFM1 level (101 ± 71 pg/mL) was observed in the 50-60 years age group. In conclusion, detection frequency and urinary AFM1 levels in the Bangladeshi adults support concerns regarding their dietary exposure to AFB1. These first data warrant further biomarker-based studies in children and in cohorts of other parts of the country.

Elevated concentrations of serum matrix metalloproteinase-2 and -9 and their associations with circulating markers of cardiovascular diseases in chronic arsenic-exposed individuals.

BACKGROUND: Cardiovascular diseases (CVDs) and cancers are the major causes of chronic arsenic exposure-related morbidity and mortality. Matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9) are deeply involved in the pathogenesis of CVDs and cancers. This study has been designed to evaluate the interactions of arsenic exposure with serum MMP-2 and MMP-9 concentrations especially in relation to the circulating biomarkers of CVDs. METHODS: A total of 373 human subjects, 265 from arsenic-endemic and 108 from non-endemic areas in Bangladesh were recruited for this study. Arsenic concentrations in the specimens were measured by inductively coupled plasma mass spectroscopy (ICP-MS) and serum MMPs were quantified by immunoassay kits. RESULTS: Serum MMP-2 and MMP-9 concentrations in arsenic-endemic population were significantly (p < 0.001) higher than those in non-endemic population. Both MMPs showed significant positive interactions with drinking water (r s = 0.208, p < 0.001 for MMP-2; r s = 0.163, p < 0.01 for MMP-9), hair (r s = 0.163, p < 0.01 for MMP-2; r s = 0.173, p < 0.01 for MMP-9) and nail (r s = 0.160, p < 0.01 for MMP-2; r s = 0.182, p < 0.001 for MMP-9) arsenic of the study subjects. MMP-2 concentrations were 1.02, 1.03 and 1.05 times, and MMP-9 concentrations were 1.03, 1.06 and 1.07 times greater for 1 unit increase in log-transformed water, hair and nail arsenic concentrations, respectively, after adjusting for covariates (age, sex, BMI, smoking habit and hypertension). Furthermore, both MMPs were increased dose-dependently when the study subjects were split into three (≤10, 10.1-50 and > 50 µg/L) groups based on the regulatory upper limit of water arsenic concentration set by WHO and Bangladesh Government. MMPs were also found to be significantly (p < 0.05) associated with each other. Finally, the concentrations of both MMPs were correlated with several circulating markers related to CVDs. CONCLUSIONS: This study showed the significant positive associations and dose-response relationships of arsenic exposure with serum MMP-2 and MMP-9 concentrations. This study also showed the interactions of MMP-2 and MMP-9 concentrations with the circulating markers of CVDs suggesting the MMP-2 and MMP-9 -mediated mechanism of arsenic-induced CVDs.

Arsenic-induced Histological Alterations in Various Organs of Mice.

Deposition of arsenic in mice through groundwater is well documented but little is known about the histological changes of organs by the metalloid. Present study was designed to evaluate arsenic-induced histological alterations in kidney, liver, thoracic artery and brain of mice which are not well documented yet. Swiss albino male mice were divided into 2 groups and treated as follows: Group 1: control, 2: arsenic (sodium arsenite at 10 mg/kg b.w. orally for 8 wks). Group 2 showed marked degenerative changes in kidney, liver, thoracic artery, and brain whereas Group 1 did not reveal any abnormalities on histopathology. We therefore concluded that arsenic induces histological alterations in the tested organs.

First results on citrinin biomarkers in urines from rural and urban cohorts in Bangladesh.

Citrinin (CIT) is a mycotoxin contaminant in food commodities and can co-occur with ochratoxin A (OTA), another nephrotoxic contaminant in food and feed. Presence of OTA in maize from Bangladesh has been reported, but no data exist on CIT occurrence in food or feed in Bangladesh. Since biomonitoring provides the best approach to assess human exposure to contaminants from various sources and by all routes, a validated method for biomarker analysis has been used to investigate the presence of CIT and its metabolite dihydrocitrinone (HO-CIT) in urines from two Bangladeshi cohorts: Both analytes were determined in urine samples collected from inhabitants of a rural (n=32) and an urban (n=37) area in the Rajshahi district of Bangladesh. After cleanup by immunoaffinity columns, extracts were analyzed by LC-MS/MS; the limits of detection for CIT and HO-CIT in urine were 0.02 and 0.05 ng/mL, respectively. CIT and HO-CIT were detectable in 94 and 71% of all urine samples. Urinary biomarker levels did not show significant correlations with age, gender, and body mass index of the donors. However, excretion of CIT together with its metabolite HO-CIT was significantly higher (p<0.01) in the rural cohort (mean 1.1±1.9 ng/mL) than in the urban cohort (mean 0.14±0.14 ng/mL). This clearly indicates differences in mycotoxin exposure. As food habits differ between rural and urban people and also their main areas of occupation, further research is needed with regard to the major contributors of CIT exposure in the two cohorts. In conclusion, this first biomarker analysis indicates widespread and variable exposure to CIT in Bangladeshi adults.

Elevated levels of plasma uric acid and its relation to hypertension in arsenic-endemic human individuals in Bangladesh.

Blood uric acid has been recognized as a putative marker for cardiovascular diseases (CVDs). CVDs are the major causes of arsenic-related morbidity and mortality. However, the association of arsenic exposure with plasma uric acid (PUA) levels in relation to CVDs has not yet been explored. This study for the first time demonstrated the associations of arsenic exposure with PUA levels and its relationship with hypertension. A total of 483 subjects, 322 from arsenic-endemic and 161 from non-endemic areas in Bangladesh were recruited as study subjects. Arsenic concentrations in the drinking water, hair and nails of the study subjects were measured by inductively coupled plasma mass spectroscopy. PUA levels were measured using a colorimetric method. We found that PUA levels were significantly (p<0.001) higher in males and females living in arsenic-endemic areas than those in non-endemic area. Arsenic exposure (water, hair and nail arsenic) levels showed significant positive correlations with PUA levels. In multiple regression analyses, arsenic exposure levels were found to be the most significant contributors on PUA levels among the other variables that included age, body mass index, blood urea nitrogen, and smoking. There were dose-response relationships between arsenic exposure and PUA levels. Furthermore, diastolic and systolic blood pressure showed significant positive correlations with PUA levels. Finally, the average PUA levels were significantly higher in the hypertensive group than those in the normotensive group in both males and females living in arsenic-endemic areas. These results suggest that arsenic exposure-related elevation of PUA levels may be implicated in arsenic-induced CVDs.