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.

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.

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.

Higher risk of hyperglycemia with greater susceptibility in females in chronic arsenic-exposed individuals in Bangladesh.

Arsenic (As) toxicity and diabetes mellitus (DM) are emerging public health concerns worldwide. Although exposure to high levels of As has been associated with DM, whether there is also an association between low and moderate As exposure and DM remains unclear. We explored the dose-dependent association between As exposure levels and hyperglycemia, with special consideration of the impact of demographic variables, in 641 subjects from rural Bangladesh. The total study participants were divided into three groups depending on their levels of exposure to As in drinking water (low, moderate and high exposure groups). Prevalence of hyperglycemia, including impaired glucose tolerance (IGT) and DM was significantly associated with the subjects' drinking water arsenic levels. Almost all exposure metrics (As levels in the subjects' drinking water, hair and nails) showed dose-dependent associations with the risk of hyperglycemia, IGT and DM. Among the variables considered, sex, age, and BMI were found to be associated with higher risk of hyperglycemia, IGT and DM. In sex-stratified analyses, As exposure showed a clearer pattern of dose-dependent risk for hyperglycemia in females than males. Finally, drinking water containing low-to-moderate levels of As (50.01-150 µg/L) was found to confer a greater risk of hyperglycemia than safe drinking water (As ≤10 µg/L). Thus the results suggested that As exposure was dose-dependently associated with hyperglycemia, especially in females.

Butyrylcholinesterase-a potential plasma biomarker in manganese-induced neurobehavioral changes.

Groundwater particularly drinking water contamination with metals has created an environmental disaster in Bangladesh. Manganese (Mn), an essential trace element, plays a key role in the development and function of the brain. Excess Mn exposure is reported to be associated with complex neurological disorders. Here, we have found a notably large extent of Mn above the permissive limit in the tube-well water of Rajshahi and Naogaon districts in Bangladesh. Higher levels of Mn in hair and nail samples, and a decreasing level of butyrylcholinesterase (BChE) activity were detected in plasma samples of the human subjects recruited from Naogaon district. Mn concentrations in water, hair, and nails were negatively correlated with the plasma BChE levels in Mn-exposed populations. To compare and validate these human studies, an animal model was used to determine the in vivo effects of Mn on neurobehavioral changes and blood BChE levels. In elevated plus maze, the time spent was significantly reduced in open arms and increased in closed arms of Mn-exposed mice compared to control group. The mean latency time to find the platform was declined significantly in control mice compared to Mn-treated group during 7 days in Morris water maze test, and Mn-exposed group also spent significantly less time in the desired quadrant as compared to the control group in probe trial. BChE activity was significantly reduced in Mn-exposed mice compared to control mice. Taken together, these results suggest that plasma BChE levels may serve as reliable biomarker of Mn-induced neurotoxicity related to behavioral changes.

Antimony-Induced Neurobehavioral and Biochemical Perturbations in Mice.

Groundwater used for drinking has been contaminated with naturally occurring inorganic arsenic and other metals, and metal-contaminated drinking water is the biggest threat to public health in Bangladesh. Toxic metals present in the drinking water have a strong relationship with chronic diseases in humans. Antimony (Sb), a naturally occurring metal, has been reported to be present in the drinking water along with other heavy metals in Bangladesh. Although Sb is present in the environment, very little attention has been given to the toxic effects of Sb. The present study was designed to investigate the in vivo effects of Sb on neurobehavioral changes like anxiety, learning and memory impairment, and blood indices related to organ dysfunction. Mice exposed to antimony potassium-tartrate hydrate (Sb) (10 mg/kg body weight) significantly (p < 0.05) decreased the time spent in open arms while increased the time spent in closed arms compared to the control mice in elevated plus maze. The mean latency time of control group to find the platform decreased (p < 0.05) significantly during 7 days learning as compared to Sb-treated group in Morris water maze test, and Sb-exposed group spent significantly (p < 0.05) less time in the desired quadrant as compared to the control group in probe trial. Sb treatment also significantly altered blood indices related to liver and kidney dysfunction. Additionally, Sb-induced biochemical alterations were associated with significant perturbations in histological architecture of liver and kidney of Sb-exposed mice. These data suggest that Sb has a toxic effect on neurobehavioral and biochemical changes in mice.

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.