Concomitant Exposure to Lower Doses of Arsenic, Lead, and Manganese Induces Greater Synergistic Neurotoxicity Than Individual Metals in Mice.

People in Bangladesh are often exposed to low to high levels of multiple metals due to contaminated groundwater with various heavy metals such as arsenic (As), lead (Pb), and manganese (Mn). However, the effects of concomitant exposure of these three metals on neurobehavioral changes are yet to be studied. Therefore, this study was intended to assess the neurotoxic effect of As, Pb, and Mn in a mouse model. Elevated plus maze (EPM) and Morris water maze (MWM) tests were conducted to evaluate anxiety, learning, and spatial memory impairment, respectively. The mice exposed to a combination of metals spent least time exploring the open arms and had longer latencies to find the hidden platform than the control and individual metal exposure groups in EPM and MWM tests. Moreover, concomitant multi-metal exposure remarkably decreased the activities of cholinergic and antioxidant enzymes, brain-derived neurotropic factor (BDNF), and nuclear factor erythroid 2-related factor 2 (Nrf2) levels and significantly increased interleukin-6 (IL-6) level in the brain tissue compared to the control and individual metal-exposed mice. Among the mice treated with a single metal, the As-treated mice showed the highest toxic effects than Pb- or Mn-treated mice. Taken together, the present study demonstrated that exposure to a mixture of As, Pb, and Mn, even at lower doses than individual metals, significantly augmented anxiety-like behavior and impaired learning and spatial memory compared to exposure to individual metals, which was associated with the changes of BDNF, Nrf2, IL-6 levels, and related enzyme activities in the brain.

Arsenic Exposure-Related Hypertension in Bangladesh and Reduced Circulating Nitric Oxide Bioavailability.

BACKGROUND: Hypertension is a major cause of death worldwide. Although arsenic exposure has been associated with the risk of hypertension, this association appears nonuniform due to inconsistent results from studies conducted in different populations. Moreover, hypertension is a complex condition with multiple underlying mechanisms and factors. One factor is impaired production and bioavailability of vascular nitric oxide (NO). However, the implications of the effects of arsenic exposure on circulating NO and its association with hypertension in humans are largely unknown. OBJECTIVE: We investigated the dose-response relationship between arsenic exposure and hypertension with vascular NO levels as a potential mediator of arsenic-related hypertension in individuals exposed to a broad range of arsenic. METHODS: A total of 828 participants were recruited from low- and high-arsenic exposure areas in Bangladesh. Participants' drinking water, hair, and nail arsenic concentrations were measured by inductively coupled plasma mass spectroscopy. Hypertension was defined as a systolic blood pressure (SBP) value of ≥140 and a diastolic (DBP) value of ≥90 mmHg. Serum NO levels reflected by total serum nitrite concentrations were measured by immunoassay. A formal causal mediation analysis was used to assess NO as a mediator of the association between arsenic level and hypertension. RESULTS: Increasing concentrations of arsenic measured in drinking water, hair, and nails were associated with the increasing levels of SBP and DBP. The odds of hypertension were dose-dependently increased by arsenic even in participants exposed to relatively low to moderate levels (10-50µg/L) of water arsenic [odds ratios (ORs) and 95% confidence intervals (CIs): 2.87 (95% CI: 1.28, 6.44), 2.67 (95% CI: 1.27, 5.60), and 5.04 (95% CI: 2.71, 9.35) for the 10-50µg/L, 50.01-150µg/L, and >150µg/L groups, respectively]. Causal mediation analysis showed a significant mediating effect of NO on arsenic-related SBP, DBP, and hypertension. CONCLUSION: Increasing exposure to arsenic was associated with increasing odds of hypertension. The association was mediated through the reduction of vascular NO bioavailability, suggesting that impaired NO bioavailability was a plausible underlying mechanism of arsenic-induced hypertension in this Bangladeshi population. https://doi.org/10.1289/EHP13018.

Fenugreek seed powder protects mice against arsenic-induced neurobehavioral changes.

The current study was designed to evaluate the protective effect of fenugreek seed powder against As-induced neurobehavioral and biochemical perturbations using a mouse model. Mice exposed to arsenic at 10 mg/kg body weight showed development of anxiety-like behavior and memory impairment compared to control mice in elevated plus maze and Morris water maze tests, respectively. A significantly decreased acetyl and butyrylcholinesterase, superoxide dismutase and glutathione reductase activities and brain-derived neurotrophic factor levels were found in the brain of arsenic-exposed mice compared to control mice. Interestingly, supplementation of fenugreek seed powder to arsenic-treated mice significantly restored the activity of cholinesterase and antioxidant enzymes (e.g. superoxide dismutase, glutathione reductase) as well as brain-derived neurotrophic factor levels in the brain tissue of arsenic-exposed mice. Consequently, reduced anxiety-like behavior, improved learning and memory were observed in fenugreek supplemented arsenic treated mice compared to only arsenic-exposed mice group. Thus, this study suggests that fenugreek seed powder reduces arsenic-induced neurotoxicity in mice.

Association between serum periostin levels and the severity of arsenic-induced skin lesions.

Arsenic is a potent environmental toxicant and human carcinogen. Skin lesions are the most common manifestations of chronic exposure to arsenic. Advanced-stage skin lesions, particularly hyperkeratosis have been recognized as precancerous diseases. However, the underlying mechanism of arsenic-induced skin lesions remains unknown. Periostin, a matricellular protein, is implicated in the pathogenesis of many forms of skin lesions. The objective of this study was to examine whether periostin is associated with arsenic-induced skin lesions. A total of 442 individuals from low- (n = 123) and high-arsenic exposure areas (n = 319) in rural Bangladesh were evaluated for the presence of arsenic-induced skin lesions (Yes/No). Participants with skin lesions were further categorized into two groups: early-stage skin lesions (melanosis and keratosis) and advanced-stage skin lesions (hyperkeratosis). Drinking water, hair, and nail arsenic concentrations were considered as the participants' exposure levels. The higher levels of arsenic and serum periostin were significantly associated with skin lesions. Causal mediation analysis revealed the significant effect of arsenic on skin lesions through the mediator, periostin, suggesting that periostin contributes to the development of skin lesions. When skin lesion was used as a three-category outcome (none, early-stage, and advanced-stage skin lesions), higher serum periostin levels were significantly associated with both early-stage and advanced-stage skin lesions. Median (IQR) periostin levels were progressively increased with the increasing severity of skin lesions. Furthermore, there were general trends in increasing serum type 2 cytokines (IL-4, IL-5, IL-13, and eotaxin) and immunoglobulin E (IgE) levels with the progression of the disease. The median (IQR) of IL-4, IL-5, IL-13, eotaxin, and IgE levels were significantly higher in the early-and advanced-stage skin lesions compared to the group of participants without skin lesions. The results of this study suggest that periostin is implicated in the pathogenesis and progression of arsenic-induced skin lesions through the dysregulation of type 2 immune response.

Clerodendrum viscosum leaves attenuate lead-induced neurotoxicity through upregulation of BDNF-Akt-Nrf2 pathway in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Clerodendrum viscosum is an important medicinal plant in Ayurveda in Bangladesh and its leaves are used as a remedy for various diseases such as anti-inflammatory, antibacterial, hyperglycemic, hepatoprotective effects. AIM OF THE STUDY: The present study aimed to evaluate the protective effect of aqueous extract of C. viscosum leaves against Pb-induced neurobehavioral and biochemical changes in mice. MATERIALS AND METHODS: Swiss albino mice were divided as a) control, b) lead treated (Pb) and c) C. viscosum leaves (Cle) d) Pb plus Cle groups. Pb-acetate (10 mg/kg body weight) was given to Pb and Pb + Cle groups mice, and water extract of leaves (50 mg/kg body weight) was provided as supplementation to Cle and Pb + Cle groups mice for 30 days. Elevated plus maze and Morris water maze tests were used for evaluating anxiety, spatial memory and learning, respectively. Status of cholinesterase, SOD, GSH enzyme activity and neurotoxicity markers such BDNF and Nrf2 levels were analyzed in the brain tissue of experimental mice. RESULTS: Poorer learning, inferior spatial memory, and increased anxiety-like behavior in Pb-exposure mice were noted when compared to control mice in Morris water maze and elevated plus maze test, respectively. In addition, expression of BDNF and Nrf2, cholinesterase activity along with antioxidant activity were significantly reduced compared to control group (p < 0.01). Interestingly, C. viscosum leaves' aqueous extract supplementation in Pb-exposed mice provide a significant improved neurochemical and antioxidant properties through the augmentation of activity of cholinergic enzymes, and upregulation of BDNF and Nrf2 levels in the brain tissue compared to Pb-exposed mice. CONCLUSIONS: This study suggested that C. viscosum leaves restore the cognitive dysfunction and reduce anxiety-like behavior through upregulation of BDNF mediated Akt-Nrf2 pathway in Pb-exposure mice.

Mulberry leaves juice attenuates arsenic-induced neurobehavioral and hepatic disorders in mice.

Arsenic (As) poisoning has caused an environmental catastrophe in Bangladesh as millions of people are exposed to As-contaminated drinking water. Chronic As-exposure causes depression, memory impairment, and liver injury in experimental animals. This study was carried out to assess the protective effect of mulberry leaves juice (Mul) against As-induced neurobehavioral and hepatic dysfunctions in Swiss albino mice. As-exposed mice spent significantly reduced time in open arms and increased time spent in closed arms in the elevated plus maze (EPM) test, whereas they took significantly longer time to find the hidden platform in the Morris water maze (MWM) test and spent significantly less time in the desired quadrant when compared to the control mice. A significant reduction in serum BChE activity, an indicator of As-induced neurotoxicity-associated behavioral changes, was noted in As-exposed mice compared to control mice. Supplementation of Mul to As-exposed mice significantly increased serum BChE activity, increased the time spent in open arms and reduced time latency to find the hidden platform, and stayed more time in the target quadrant in EPM and MWM tests, respectively, compared to As-exposed-only mice. Also, a significantly reduced activity of BChE, AChE, SOD, and GSH in brain, and elevated ALP, AST, and ALT activities in serum were noted in As-exposed mice when compared to control mice. Mul supplementation significantly restored the activity of these enzymes and also recovered As-induced alterations in hepatic tissue in As-exposed mice. In conclusion, this study suggested that mulberry leaves juice attenuates As-induced neurobehavioral and hepatic dysfunction in mice.

Performance of a hermetic device and neem (Azadirachta indica) in storing wheat seed: Evidence from participatory household trials in central Bangladesh.

Smallholder farmers in Bangladesh often use low-density polyethylene (LDPE) bags contained within woven polypropylene bags to store wheat seed during the summer monsoon that precedes winter season planting. High humidity and temperature during this period can encourage increased seed moisture and pests, thereby lowering seed quality. Following a farm household survey conducted to inform trial design, eighty farmers were engaged in an action research process in which they participated in designing and conducting trials comparing traditional and alternative seed storage methods over 30 weeks. Factorial treatments included comparison of hermetic SuperGrainbags® (Premium RZ) against LDPE bags, both with and without the addition of dried neem tree leaves (Azadirachta indica). SuperGrainbags® were more effective in maintaining seed moisture at acceptable levels close to pre-storage conditions than LDPE bags. Both seed germination and seedling coleoptile length were significantly greater in hermetic than LDPE bags. Neem had no effect on seed moisture, germination, or coleoptile length. SuperGrainbags® were also more effective in abating seed damage during storage, although inclusion of neem within LDPE bags also had significant damage. Quantification of seed predating insects and diseases suggested that SuperGrainbags® also suppressed Coleopteran pests and blackspot, the latter indicative of Fusarium graminearum. Conversely, where farmers used LDPE bags, neem also had an additional though limited pest suppressive effect. Post-storage treatment scoring by farmers revealed a strong preference for SuperGrainbags® and no preference differences for or against neem. This study demonstrates a process by which farmers can be involved in the participatory co-design and testing of alternative wheat storage options, and stresses the need to develop SuperGrainbag® supply chains so hermetic storage can be made widely available.

Seroprevalence of SARS-CoV-2 antibodies in Bangladesh related to novel coronavirus infection.

Design: A cross-sectional study was conducted amongst household members in 32 districts of Bangladesh to build knowledge about disease epidemiology and seroepidemiology of coronavirus disease 2019 (COVID-19). Objective: Antibody responses to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) were assessed in people between April and October 2020. Results: The national seroprevalence rates of immunoglobulin G (IgG) and IgM were estimated to be 30.4% and 39.7%, respectively. In Dhaka, the seroprevalence of IgG was 35.4% in non-slum areas and 63.5% in slum areas. In areas outside of Dhaka, the seroprevalence of IgG was 37.5% in urban areas and 28.7% in rural areas. Between April and October 2020, the highest seroprevalence rate (57% for IgG and 64% for IgM) was observed in August. IgM antibody was more prevalent in younger participants, while older participants had more frequent IgG seropositivity. Follow-up specimens from patients with COVID-19 and their household members suggested that both IgG and IgM seropositivity increased significantly at day 14 and day 28 compared with day 1 after enrolment. Conclusions: SARS-CoV-2 had spread extensively in Bangladesh by October 2020. This highlights the importance of monitoring seroprevalence data, particularly with the emergence of new SARS-CoV-2 variants over time.

Elevated serum periostin levels among arsenic-exposed individuals and their associations with the features of asthma.

Chronic exposure to arsenic via drinking water is a serious public health issue in many countries. Arsenic causes not only cancers but also non-malignant diseases, including asthma. We have previously reported that arsenic exposure increases the risk of Th2-mediated allergic asthma. The serum level of periostin, an extracellular matrix protein activated by Th2 cytokines, is recognized as a biomarker for Th2-mediated eosinophilic asthma and contributes to enhanced airway inflammation and remodeling. However, the role of periostin in arsenic-related asthma is unknown. Therefore, this study was designed to explore the associations of serum periostin levels with arsenic exposure and the features of asthma in 442 individuals in Bangladesh who participated in our previous study. Exposure levels of the participants were determined by measuring the arsenic concentrations in drinking water, hair, and nails through inductively coupled plasma mass spectroscopy. Periostin levels in serum were assessed by immunoassay. In this study, we found that serum periostin levels of the participants were increased with increasing exposure to arsenic. Notably, even the participants with 10.1-50 µg/L arsenic in drinking water had significantly higher levels of periostin than participants with <10 µg/L of water arsenic. Elevated serum periostin levels were positively associated with serum levels of Th2 mediators, such as interleukin (IL)-4, IL-5, IL-13, and eotaxin. Each log increase in periostin levels was associated with approximately eight- and three-fold increases in the odds ratios (ORs) for reversible airway obstruction (RAO) and asthma symptoms, respectively. Additionally, causal mediation analyses revealed that arsenic exposure metrics had both direct and indirect (periostin-mediated) effects on the risk of RAO and asthma symptoms. Thus, the results suggested that periostin may be involved in the arsenic-related pathogenesis of Th2-mediated asthma. The elevated serum periostin levels may predict the greater risk of asthma among the people living in arsenic-endemic areas.

Parental Lead Exposure Promotes Neurobehavioral Disorders and Hepatic Dysfunction in Mouse Offspring.

Lead (Pb) induces neurotoxicity in both children and adults. Children are more vulnerable to Pb toxicity than adults. Little is known about the effects of Pb on the mental health of the children who are prenatally exposed. Therefore, we designed an animal experiment to compare the adverse effects of Pb on neurobehavioral and hepatic functions between Pb-exposed (Pb mice) and parental Pb-exposed (P-Pb mice) group mice. Mice were treated with Pb-acetate (10 mg/kg bodyweight/day) via drinking water. Male mice from unexposed parents treated with Pb for 90 days were defined as Pb mice, whereas male mice from Pb-exposed parents treated with Pb for further 90 days were defined as P-Pb mice. Anxiety-like behavior and spatial memory and learning were assessed by elevated plus maze and Morris water maze. Serum hepatic enzyme activities and butyrylcholinesterase activity were measured by an analyzer. P-Pb mice displayed increased anxiety-like behavior and memory and learning impairments compared to Pb mice. BChE activity was significantly decreased in P-Pb mice compared to Pb mice. Pb levels in the brains of P-Pb mice were significantly higher than those of Pb mice. The activities of serum hepatic enzymes of P-Pb mice were also higher than those of Pb mice. Additionally, histopathology data revealed that hepatic tissue injury was more pronounced in P-Pb mice than in Pb mice. Thus, the results suggest that persistent exposure to Pb from fetus to adult causes more severe neurobehavioral changes and hepatic toxicities than adult exposure only.

Arsenic Secondary Methylation Capacity Is Inversely Associated with Arsenic Exposure-Related Muscle Mass Reduction.

Skeletal muscle mass reduction has been implicated in insulin resistance (IR) that promotes cardiometabolic diseases. We have previously reported that arsenic exposure increases IR concomitantly with the reduction of skeletal muscle mass among individuals exposed to arsenic. The arsenic methylation capacity is linked to the susceptibility to some arsenic exposure-related diseases. However, it remains unknown whether the arsenic methylation capacity affects the arsenic-induced reduction of muscle mass and elevation of IR. Therefore, this study examined the associations between the arsenic methylation status and skeletal muscle mass measures with regard to IR by recruiting 437 participants from low- and high-arsenic exposure areas in Bangladesh. The subjects' skeletal muscle mass was estimated by their lean body mass (LBM) and serum creatinine levels. Subjects' drinking water arsenic concentrations were positively associated with total urinary arsenic concentrations and the percentages of MMA, as well as inversely associated with the percentages of DMA and the secondary methylation index (SMI). Subjects' LBM and serum creatinine levels were positively associated with the percentage of DMA and SMI, as well as inversely associated with the percentage of MMA. HOMA-IR showed an inverse association with SMI, with a confounding effect of sex. Our results suggest that reduced secondary methylation capacity is involved in the arsenic-induced skeletal muscle loss that may be implicated in arsenic-induced IR and cardiometabolic diseases.

T helper 2-driven immune dysfunction in chronic arsenic-exposed individuals and its link to the features of allergic asthma.

Limited information is available regarding the effects of arsenic exposure on immune function. We have recently reported that chronic exposure to As was associated asthma, as determined by spirometry and respiratory symptoms. Because T helper 2 (Th2)-driven immune responses are implicated in the pathogenesis of allergic diseases, including asthma, we studied the associations of serum Th1 and Th2 mediators with the As exposure markers and the features of asthma among individuals exposed to As. A total of 553 blood samples were selected from the same study subjects recruited in our previous asthma study. Serum levels of Th1 and Th2 cytokines were analyzed by immunoassay. Subjects' arsenic exposure levels (drinking water, hair and nail arsenic concentrations) were determined by inductively coupled plasma mass spectroscopy. Arsenic exposure levels of the subjects showed significant positive associations with serum Th2-mediators- interleukin (IL)-4, IL-5, IL-13, and eotaxin without any significant changes in Th1 mediators- interferon-γ and tumor necrosis factor-α. The ratios of Th2 to Th1 mediators were significantly increased with increasing exposure to As. Notably, most of the Th2 mediators were positively associated with serum levels of total immunoglobulin E and eotaxin. The serum levels of Th2 mediators were significantly higher in the subjects with asthma than those without asthma. The results of our study suggest that the exacerbated Th2-driven immune responses are involved in the increased susceptibility to allergic asthma among individuals chronically exposed to As.

Exposure to air pollution and COVID-19 severity: A review of current insights, management, and challenges.

Several epidemiological studies have suggested a link between air pollution and respiratory tract infections. The outbreak of coronavirus disease 2019 (COVID-19) poses a great threat to public health worldwide. However, some parts of the globe have been worse affected in terms of prevalence and deaths than others. The causes and conditions of such variations have yet to be explored. Although some studies indicated a possible correlation between air pollution and COVID-19 severity, there is yet insufficient data for a meaningful answer. This review summarizes the impact of air pollution on COVID-19 infections and severity and discusses the possible management strategies and challenges involved. The available literature investigating the correlation between air pollution and COVID-19 infections and mortality are included in the review. The studies reviewed here suggest that exposure to air pollution, particularly to PM2.5 and NO2 , is positively correlated with COVID-19 infections and mortality. Some data indicate that air pollution can play an important role in the airborne transmission of SARS-CoV-2. A high percentage of COVID-19 incidences has been reported in the most polluted areas, where patients needed hospital admission. The available data also show that both short-term and long-term air pollution may enhance COVID-19 severity. However, most of the studies that showed a link between air pollution and COVID-19 infections and mortality did not consider potential confounders during the correlation analysis. Therefore, more specific studies need to be performed focusing on some additional confounders such as individual age, population density, and pre-existing comorbidities to determine the impact of air pollution on COVID-19 infections and deaths. Integr Environ Assess Manag 2021;17:1114-1122. © 2021 SETAC.

Multi-year weed community dynamics and rice yields as influenced by tillage, crop establishment, and weed control: Implications for rice-maize rotations in the eastern Gangetic plains.

In South Asia's rice-based cropping systems, most farmers flood and repetitively till their fields before transplanting. This establishment method, commonly termed puddled transplanted rice (TPR), is costly. In addition, it is labor and energy intensive. To increase labor and energy efficiency in rice production, reduced or zero-tilled direct seeded rice (ZT-DSR) is commonly proposed as an alternative tillage and crop establishment (TCE) option. Effective management of weeds in ZT-DSR however remains a major challenge. We conducted a four-year experiment under a rice-maize rotation in Northwestern Bangladesh in the eastern Gangetic Plains to examine the performance of two TCE methods and three weed management regimes (WMR) on the diversity and competitiveness of weed communities in the rice phase of the rotation. The Shannon-Weiner Diversity Index, a measure of species diversity, was significantly greater under ZT-DSR than puddled TPR. It was also greater under no weed control (Weedy) and two manual weeding (MW) treatments compared to chemical herbicide with manual weeding (C + MW). In DSR Weedy plots, weed communities began shifting from grasses to sedges from the rotation's second year, while in the ZT-DSR and C + MW treatments, sedges were consistently predominant. In both puddled TPR Weedy and TPR C + MW treatments, broadleaves and grasses were dominant in the initial year, while sedges dominated in the final year. There were significant main effects of year (Y) and weed management regime (WMR), but not of TCE. Significant Y × TCE and TCE × WMR interaction effects on rice yield were also observed. Grain yields under ZT-DSR were similar to puddled TPR. ZT-DSR with one application of pre-emergence herbicide followed by one hand weeding at 28 days after establishment however resulted in significantly higher grain yield (5.34 t ha-1) compared the other weed management regimes. Future research should address methods to effectively manage weed community composition shifts in both ZT-DSR and TPR under rice-maize rotations utilizing integrated and low-cost strategies that can be readily applied by farmers in the eastern Gangetic Plains.

Liver injury in severe COVID-19 infection: current insights and challenges.

INTRODUCTION: The outbreak of COVID-19 is a serious health threat worldwide. Different degrees of liver injury or liver dysfunctions have been reported in patients with COVID-19 infection. However, currently, it remains unclear to what extent liver diseases should be considered as significant risk factors for the severity and mortality of COVID-19. Moreover, the mechanisms involved in liver injury in severe COVID-19 infection are not yet well understood. AREA COVERED: This review summarizes the current evidence on liver function abnormalities in COVID-19 patients and the effects of preexisting liver disease on the disease severity. This review also illustrates the possible underlying mechanisms linking COVID-19 to liver injury, as well as provides recommendations to prevent liver damage in COVID-19 infection. EXPERT OPINION: The elevated levels of ALT, AST, GGT and bilirubin are common in more severe patients than non-severe or mild COVID-19 patients. Patients with preexisting medical conditions including chronic hepatic diseases are at higher risk for severe illness from COVID-19 infection. The drug's effects, possible viral inclusion in liver cells, systemic inflammation and hypoxia are potential causes of liver injury in severe COVID-19. Nevertheless, further studies are needed focusing on the preexisting hepatic diseases on prevention, treatment and outcome of COVID-19.

Arsenic exposure-related hyperglycemia is linked to insulin resistance with concomitant reduction of skeletal muscle mass.

BACKGROUND: Alargebodyof evidence has shown a link between arsenic exposure and diabetes, but the underlying mechanisms have not yet been clarified. OBJECTIVE: We explored the association between arsenic exposure and the reduction of skeletal muscle mass as a potential mechanism of insulin resistance for developing arsenic-related hyperglycemia. METHODS: A total of 581 subjects were recruited from arsenic-endemic and non-endemic areas in Bangladesh and their fasting blood glucose (FBG), serum insulin, and serum creatinine levels were determined. Subjects' arsenic exposure levels were assessed by arsenic concentrations in water, hair, and nails. HOMA-IR and HOMA-ß were used to calculate insulin resistance and ß-cell dysfunction, respectively. Serum creatinine levels and lean body mass (LBM) were used as muscle mass indicators. RESULTS: Water, hair and nail arsenic concentrations showed significant positive associations with FBG, serum insulin and HOMA-IR and inverse associations with serum creatinine and LBM in a dose-dependent manner both in males and females. Water, hair and nail arsenic showed significant inverse associations with HOMA-ß in females but not in males. FBG and HOMA-IR were increased with the decreasing levels of serum creatinine and LBM. Odds ratios (ORs)of hyperglycemia were significantly increased with the increasing concentrations of arsenic in water, hair and nails and with the decreasing levels of serum creatinine and LBM. Females' HOMA-IR showed greater susceptibility to the reduction of serum creatinine and LBM, possibly causing the greater risk of hyperglycemia in females than males. Path analysis revealed the mediating effect of serum creatinine level on the relationship of arsenic exposure with HOMA-IR and hyperglycemia. CONCLUSION: Arsenic exposure elevates FBG levels and the risk of hyperglycemia through increasing insulin resistance with greater susceptibility in females than males. Additionally, arsenic exposure-related reduction of skeletal muscle mass may be a mechanism underlying the development of insulin resistance and hyperglycemia.

Association between chronic arsenic exposure and the characteristic features of asthma.

Widespread contamination of arsenic (As) has become a global public health concern. Exposure to As causes respiratory complications. Asthma, a major respiratory complication, is increasing worldwide. However, the effect of chronic As exposure on the risk of asthma remains to be clarified. This study aims to examine the associations between As exposure (water, hair and nail As) and the risk of asthma among 842 individuals exposed to a wide range of As concentrations through drinking water in Bangladesh. Subjects' As exposure levels were measured with ICP-MS. Lung function was examined by a handheld spirometer. Characteristic features of asthma were evaluated by bronchodilator-mediated reversibility in airway obstruction and asthma-like symptoms through a structured questionnaire. Total serum immunoglobulin E (sIgE) levels were measured by immunoassay. As exposure metrics showed inverse associations with lung function measures (FEV1, FEV6, and FEV1/FEV6 ratio) and positive associations with the risks of airway obstruction (AO), reversible airway obstruction (RAO), and asthma-like symptoms. The majority of AO patients (70 of 97) were RAO with one or more characteristic symptoms of asthma. Intriguingly, subjects' As exposure levels showed positive associations with total sIgE levels. Total sIgE in RAO patients was significantly (p < 0.001) higher than that in the control group. Thus the results revealed that chronic As exposure was associated with the risk of the characteristic features of asthma. Additionally the association between As exposure and subjects' total sIgE levels and an elevated level of total sIgE in RAO group suggested that As exposure-related asthma might be allergic in nature.

In vivo evaluation of arsenic-associated behavioral and biochemical alterations in F0 and F1 mice.

Groundwater contaminated with arsenic (As) is the biggest threat to public health in Bangladesh. The children of As-exposure parents are also exposing to As through drinking water. The effects of As on the children's health of As-exposure parents are poorly understood. An animal study was taken to evaluate the effects of As on behavioral and biochemical changes in F1 mice. Swiss albino mice were separated into three groups: a) control, b) As-treated F0 and c) As-treated F1. Elevated plus maze and Morris water maze tests were used for evaluating anxiety, spatial memory and learning, respectively. We found that the effect of As on anxiety like behavior, spatial memory and learning impairment in As-treated F1 mice was significantly higher than that of As-treated F0 mice and control group. Additionally, we also evaluated the effects of As on biochemical parameters by measuring ALT, AST, ALP, BChE, SOD activities and the level of creatinine in As-induced mice, where we found that all of the blood parameters were significantly changed in F1 generation. A significant portion of As accumulated in the brain, liver and kidney of F1 mice than F0 mice. Histological analysis revealed a significant change in tissue damage related to hepatic and renal dysfunctions that might be associated with As-induced biochemical alterations. In conclusion, arsenic plays an important role for the development of As-associated neurological disorders, hepatic toxicities, and renal dysfunctions in both F0 and F1 generations. Notably F1 mice were much more vulnerable to As-exposure than F0 mice.

Manganese attenuates the effects of arsenic on neurobehavioral and biochemical changes in mice co-exposed to arsenic and manganese.

An unsafe level of manganese (Mn) was detected in the drinking water in some arsenic (As)-contaminated areas in Bangladesh. Mn is an essential trace element; however, the intake of a higher level of Mn through the drinking water is associated with the development of toxicity in humans. This study was designed to evaluate the effects of As and Mn co-exposure on neurobehavioral and biochemical alterations in a mouse model. Sodium arsenite (10 mg/kg body weight) and manganese chloride tetrahydrate (10 mg/kg body weight) were given to mice individually and in combination with drinking water for 90 days. Results showed that individual As and Mn exposure as well as co-exposure of As and Mn significantly (p < 0.05) reduced the percent of time spent in the open arms when compared with that of control mice. In addition, percent of time spent in open arms significantly (p < 0.05) increased in co-exposed mice compared with As exposure in elevated plus maze (42.05 ± 1.10 versus 38.94 ± 0.66). In the Morris water maze test, the mean time latency to find the platform was longer in metal-treated mice in comparison to that of control mice (p < 0.05). Importantly, the co-exposed group had shorter time when compared with the As-exposed group during the training periods (p < 0.05). Moreover, co-exposed mice stayed significantly (p < 0.05) more time in the target quadrant in the probe trial in comparison with that of As-exposed mice (27.25 ± 1.21 versus 23.83 ± 0.87 s) but less time than control mice (27.25 ± 1.21 versus 43.17 ± 1.49 s). In addition, a significant (p < 0.05) alteration of biochemical parameters such as ALT, AST, ALP, BChE, and SOD as well as urea and creatinine levels were noted in the As-exposed group compared with the control group and Mn significantly (p < 0.05) attenuated the effects of As in co-exposed mice. Therefore, the results of this study suggest that As and Mn may have some antagonistic effect and Mn could attenuate the As-induced neurobehavioral and biochemical alterations in co-exposed mice.

Dose-dependent relationships between chronic arsenic exposure and cognitive impairment and serum brain-derived neurotrophic factor.

BACKGROUND: Arsenic poisoning is a public health problem worldwide. A few studies have reported the effects of arsenic exposure on adult cognitive function, but with limitations in the subject selection and exposure markers. Moreover, information regarding the association between arsenic exposure and biomarker of cognitive impairment is scarce. OBJECTIVES: We examined the associations between arsenic exposure and adult cognitive impairment using the Mini-Mental State Examination (MMSE) and the serum levels of brain-derived neurotrophic factor (BDNF), a potential biomarker of cognitive health status. METHODS: We designed a cross-sectional study that recruited 693 adult (18-60 years old) subjects from the areas of low- and high­arsenic exposure in rural Bangladesh. The subjects' arsenic exposure levels (drinking water, hair, and nail arsenic concentrations) were measured by inductively coupled plasma-mass spectroscopy. The Bangla version of the MMSE was used as a cognitive assessment tool. Serum BDNF (sBDNF) levels were assessed by immunoassay. RESULTS: In this study, we found that average MMSE score and sBDNF level of the subjects in arsenic-endemic areas were significantly (p < 0.001 for both) lower than those of the subjects in non-endemic area. Our analyses revealed that both MMSE scores and sBDNF levels were decreased with the increasing concentrations of arsenic in drinking water, hair, and nails in a dose-dependent fashion. In regression analyses, significant associations of arsenic exposure metrics with MMSE scores and sBDNF levels were observed even after adjustment for several variables. Intriguingly, MMSE scores showed a significantly positive correlation with sBDNF levels. CONCLUSION: Our findings demonstrate that chronic exposure to arsenic dose-dependently decreases cognitive function in adults, with a concomitant reduction of sBDNF levels. A decreased BDNF level may be part of the biochemical basis of chronic arsenic exposure-related cognitive impairment.