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.

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.

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.

Chronic exposure to arsenic, LINE-1 hypomethylation, and blood pressure: a cross-sectional study in Bangladesh.

BACKGROUND: Chronic exposure to arsenic is associated with cancer and hypertension. Growing evidence suggests that altered methylation in long interspersed nuclear element-1 (LINE-1) is involved in many types of disorders, including cardiovascular disease. Here we evaluated the association between arsenic exposure and LINE-1 methylation levels, especially in relation to blood pressure (BP). METHODS: A total of 236 subjects (175 from arsenic-endemic areas and 61 from a non-endemic area) in rural Bangladesh were recruited. The subjects' arsenic exposure levels (i.e., drinking water, hair and nail arsenic concentrations) were measured by inductively coupled plasma mass spectroscopy. The subjects' LINE-1 methylation levels were determined by pyrosequencing. RESULTS: The average LINE-1 methylation levels of the subjects living in the arsenic-endemic areas were significantly (p < 0.01) lower than those of the subjects living in the non-endemic area. In a sex-stratified analysis, the arsenic exposure levels in female but not male subjects showed a significant inverse association with LINE-1 methylation levels before (water arsenic: p < 0.01, hair arsenic: p < 0.05, nail arsenic: p < 0.001) and after (water arsenic: p < 0.01, hair arsenic: p < 0.05, nail arsenic: p < 0.001) adjustment for age, body mass index and smoking. Analyses examining interactions among arsenic levels, BP and LINE-1 methylation showed that arsenic-related elevated levels of BP were associated with LINE-1 hypomethylation. CONCLUSIONS: Our findings demonstrated that chronic exposure to arsenic was inversely associated with LINE-1 methylation levels in blood leukocyte DNA and this was more pronounced in females than males; in addition, the decreased levels of LINE-1 methylation might be involved in the arsenic-induced elevation of BP.

Amelioration of arsenic-induced toxic effects in mice by dietary supplementation of Syzygium cumini leaf extract.

Arsenic created a serious public health problem in Bangladesh due to its presence in groundwater and dissemination of the toxic effects to millions of people. The scarcity of the treatment options to manage this affected population has made the situation much worse. To find a promising treatment option, this study was undertaken to examine the ameliorating roles of Syzygium cumini leaf extract (SLE) against arsenic-induced toxic effects in mice. Swiss albino mice were divided into four groups where 'control' group received pure water + normal feed, 'arsenic (As)' group received sodium arsenite (NaAsO2)-containing water (10 µg/g body weight/day) + normal feed, 'As+SLE' group received NaAsO2-containing water + feed supplemented with SLE (50 µg/g body weight/day) and finally the 'SLE' group received pure water + feed supplemented with SLE. A gradual increase in body weight gain was observed in control mice; however, the body weight gain in As-exposed mice was decreased. This decrease in body weight gain was prevented in As+SLE group mice that received SLE supplemented feed. Arsenic showed a secondary effect by causing enlargement of spleen, kidney and liver of 'As' group mice and this enlargement of the organs was minimized with SLE supplementation. In addition, SLE abrogated arsenic-mediated elevation of serum alkaline phosphatase (ALP), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), uric acid and glucose. These results, therefore, suggest that SLE might have future therapeutic value for preventing or reducing arsenic-induced toxic effects.

Urinary biomarkers of ochratoxin A and citrinin exposure in two Bangladeshi cohorts: follow-up study on regional and seasonal influences.

Biomonitoring studies can provide valuable insights into human mycotoxin exposure, especially when food contaminant data are scarce or unavailable as in Bangladesh. First biomonitoring data in Bangladeshi adults indicated exposure to the nephrotoxic mycotoxins ochratoxin A (OTA) and citrinin (CIT). This led us to conduct a follow-up study with analysis of urinary biomarkers for both CIT and OTA to investigate regional and seasonal influences on mycotoxin exposure in two Bangladeshi cohorts. In total, 164 urines were collected (n = 69 in summer, n = 95 in winter) from residents of a rural and an urban area, among which there were 62 participants enrolled in both sampling periods. Most urines had detectable biomarker levels (OTA, CIT and its metabolite dihydrocitrinone, HO-CIT), with more or less pronounced differences with regard to season and region. In both cohorts, OTA was found at a mean level of 0.06 ± 0.10 ng/mL urine (range 0.01-0.55 ng/mL) in summer and a mean of 0.19 ± 0.38 ng/mL (range 0.01-1.75 ng/mL) in winter season. A season difference was significant in the rural cohort, but not in the urban cohort, and slightly higher mean OTA levels in the rural compared to the urban cohort were only observed in winter urines. CIT biomarkers showed more pronounced variations, with a CIT mean of 0.10 ± 0.17 ng/mL (range 0.02-1.22 ng/mL) and HO-CIT mean of 0.42 ± 0.98 ng/mL (range 0.02-5.39 ng/mL) in summer, and CIT mean of 0.59 ± 0.98 ng/mL (range 0.05-5.03 ng/mL) and HO-CIT mean of 3.18 ± 8.49 ng/mL (range 0.02-46.44 ng/mL) in winter urines of both cohorts. In both seasons, total CIT biomarker concentrations were significantly higher in the rural cohort than in the urban cohort. A provisional daily intake for CIT was calculated and exceeded a preliminary value set by EFSA (0.2 µg/kg/d) in 10 and 24 % of participants in summer and winter, respectively. No significant correlations were found between urinary biomarker levels and intake of certain types of food, except for a positive trend for higher rice consumption. Our results in the Bangladeshi population indicate frequent co-exposure to nephrotoxic mycotoxin food contaminants that vary by season and region.

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.

Bioremediation of hexavalent chromium (VI) by a soil-borne bacterium, Enterobacter cloacae B2-DHA.

Chromium and chromium containing compounds are discharged into the nature as waste from anthropogenic activities, such as industries, agriculture, forest farming, mining and metallurgy. Continued disposal of these compounds to the environment leads to development of various lethal diseases in both humans and animals. In this paper, we report a soil borne bacterium, B2-DHA that can be used as a vehicle to effectively remove chromium from the contaminated sources. B2-DHA is resistant to chromium with a MIC value of 1000 µg mL(-1) potassium chromate. The bacterium has been identified as a Gram negative, Enterobacter cloacae based on biochemical characteristics and 16S rRNA gene analysis. TOF-SIMS and ICP-MS analyses confirmed intracellular accumulation of chromium and thus its removal from the contaminated liquid medium. Chromium accumulation in cells was 320 µg/g of cells dry biomass after 120-h exposure, and thus it reduced the chromium concentration in the liquid medium by as much as 81%. Environmental scanning electron micrograph revealed the effect of metals on cellular morphology of the isolates. Altogether, our results indicate that B2-DHA has the potential to reduce chromium significantly to safe levels from the contaminated environments and suggest the potential use of this bacterium in reducing human exposure to chromium, hence avoiding poisoning.

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.

Isolation and characterization of a Lysinibacillus strain B1-CDA showing potential for bioremediation of arsenics from contaminated water.

The main objective of this study was to identify and isolate arsenic resistant bacteria that can be used for removing arsenic from the contaminated environment. Here we report a soil borne bacterium, B1-CDA that can serve this purpose. B1-CDA was isolated from the soil of a cultivated land in Chuadanga district located in the southwest region of Bangladesh. The morphological, biochemical and 16S rRNA analysis suggested that the isolate belongs to Lysinibacillus sphaericus. The minimum inhibitory concentration (MIC) value of the isolate is 500 mM (As) as arsenate. TOF-SIMS and ICP-MS analysis confirmed intracellular accumulation and removal of arsenics. Arsenic accumulation in cells amounted to 5.0 mg g(-1) of the cells dry biomass and thus reduced the arsenic concentration in the contaminated liquid medium by as much as 50%. These results indicate that B1-CDA has the potential for remediation of arsenic from the contaminated water. We believe the benefits of implementing this bacterium to efficiently reduce arsenic exposure will not only help to remove one aspect of human arsenic poisoning but will also benefit livestock and native animal species. Therefore, the outcome of this research will be highly significant for people in the affected area and also for human populations in other countries that have credible health concerns as a consequence of arsenic-contaminated water.

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.

Elevated levels of plasma Big endothelin-1 and its relation to hypertension and skin lesions in individuals exposed to arsenic.

Chronic arsenic (As) exposure affects the endothelial system causing several diseases. Big endothelin-1 (Big ET-1), the biological precursor of endothelin-1 (ET-1) is a more accurate indicator of the degree of activation of the endothelial system. Effect of As exposure on the plasma Big ET-1 levels and its physiological implications have not yet been documented. We evaluated plasma Big ET-1 levels and their relation to hypertension and skin lesions in As exposed individuals in Bangladesh. A total of 304 study subjects from the As-endemic and non-endemic areas in Bangladesh were recruited for this study. As concentrations in water, hair and nails were measured by Inductively Coupled Plasma Mass Spectroscopy (ICP-MS). The plasma Big ET-1 levels were measured using a one-step sandwich enzyme immunoassay kit. Significant increase in Big ET-1 levels were observed with the increasing concentrations of As in drinking water, hair and nails. Further, before and after adjusting with different covariates, plasma Big ET-1 levels were found to be significantly associated with the water, hair and nail As concentrations of the study subjects. Big ET-1 levels were also higher in the higher exposure groups compared to the lowest (reference) group. Interestingly, we observed that Big ET-1 levels were significantly higher in the hypertensive and skin lesion groups compared to the normotensive and without skin lesion counterpart, respectively of the study subjects in As-endemic areas. Thus, this study demonstrated a novel dose-response relationship between As exposure and plasma Big ET-1 levels indicating the possible involvement of plasma Big ET-1 levels in As-induced hypertension and skin lesions.

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.

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.

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.