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Fluoride and arsenic are two common inorganic contaminants in drinking water that are associated with impairment in child development and retarded intelligence. The present study was conducted to explore the effects on spatial learning, memory, glutamate levels, and group I metabotropic glutamate receptors (mGluRs) expression in the hippocampus and cortex after subchronic exposure to fluoride, arsenic, and a fluoride and arsenic combination in rats. Weaned male Sprague-Dawley rats were assigned to four groups. The control rats drank tap water. Rats in the three exposure groups drank water with sodium fluoride (120 mg/L), sodium arsenite (70 mg/L), and a sodium fluoride (120 mg/L) and sodium arsenite (70 mg/L) combination for 3 months. Spatial learning and memory was measured in Morris water maze. mGluR1 and mGluR5 mRNA and protein expression in the hippocampus and cortex was detected using RT-PCR and Western blot, respectively. Compared with controls, learning and memory ability declined in rats that were exposed to fluoride and arsenic both alone and combined. Combined fluoride and arsenic exposure did not have a more pronounced effect on spatial learning and memory compared with arsenic and fluoride exposure alone. Compared with controls, glutamate levels decreased in the hippocampus and cortex of rats exposed to fluoride and combined fluoride and arsenic, and in cortex of arsenic-exposed rats. mGluR5 mRNA and protein expressions in the hippocampus and mGluR5 protein expression in the cortex decreased in rats exposed to arsenic alone. Interestingly, compared with fluoride and arsenic exposure alone, fluoride and arsenic combination decreased mGluR5 mRNA expression in the cortex and protein expression in the hippocampus, suggesting a synergistic effect of fluoride and arsenic. These data indicate that fluoride and arsenic, either alone or combined, can decrease learning and memory ability in rats. The mechanism may be associated with changes of glutamate level and mGluR5 expression in cortex and hippocampus.

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

A rapid and sensitive method was established for arsenic (As) speciation based on high performance liquid chromatography coupled to inductively coupled plasma mass spectrometry (HPLC-ICP-MS). This method was validated for the quantification of four arsenic species, including arsenite (AsIII), arsenate (AsV), monomethylarsonic acid (MMAV) and dimethylarsinic acid (DMAV) in cynomolgus macaque plasma. Separation was achieved in just 3.7 min with an alkyl reverse phase column and highly aqueous mobile phase containing 20 mM citric acid and 5 mM sodium hexanesulfonate (pH = 4.3). The calibration curves were linear over the range of 5–500 ng·mL−1 (measured as As), with r > 0.99. The above method was validated for selectivity, precision, accuracy, matrix effect, recovery, carryover effect and stability, and applied in a comparative pharmacokinetic study of arsenic species in cynomolgus macaque samples following intravenous and intragastrical administration of arsenic trioxide solution (0.80 mg·kg−1; 0.61 mg·kg−1 of arsenic); in addition, the absolute oral bioavailability of the active ingredient AsIII of arsenic trioxide in cynomolgus macaque samples was derived as 60.9 ± 16.1%.

Although studies have shown that arsenic exposure can induce apoptosis in a variety of cells, the exact molecular mechanism of chronic arsenicosis remains unclear. Based on our previous study on human serum, the present study was to determine whether pigment epithelium-derived factor (PEDF) plays a role in the damage induced by chronic arsenic exposure in a rat model and to explore the possible signaling pathway involved. Thirty male Wistar rats were randomly divided into three groups and the arsenite doses administered were 0, 10, and 50 mg/L, respectively. The experiment lasted for 6 months. Our results showed that level of arsenic increased significantly in serum, liver, brain, and kidney in arsenic-exposed groups. It was indicated that PEDF protein was widely distributed in the cytoplasm of various types of cells in liver, brain, and kidney. PEDF protein level was only changed when the arsenite dose reached 50 mg/L in liver and brain, whereas it was not changed in the kidney. In order to investigate the possible mechanism of PEDF-exerted damages upon arsenite exposure, apoptosis in liver and brain was assessed. The proportion of apoptotic cells gradually increased with increasing arsenic administration. The ratio of Bax/Bcl-2 in the high arsenic group (50 mg/L) was significantly higher than that in the control group. Therefore, we thought PEDF played a role in cell apoptosis of liver and brain which induced by sodium arsenite exposure, and the results also demonstrated that Bax and Bcl-2 might be two key targets in the action of PEDF.

The present study was conducted to investigate the protective effects of hesperidin (HSP) against sodium arsenite (SA)-induced nephrotoxicity and hepatotoxicity in rats. Thirty-five male Sprague Dawley rats were divided into five groups as follows: control, HSP, SA, SA + HSP 100, and SA + HSP 200. Rats were orally gavaged with SA (10 mg/kg body weight) and HSP (100 and 200 mg/kg body weight) for 15 days. SA increased oxidative damage by decreasing antioxidant enzyme activities, such as catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx), and glutathione (GSH) level and increasing malondialdehyde (MDA) level in the kidney and liver tissues. In addition, it increased serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities and serum urea and creatinine levels. Furthermore, SA caused inflammation, apoptosis, and oxidative DNA damage by increasing tumor necrosis factor-α (TNF-α), nuclear factor kappa B (NF-κB), interleukin-1β (IL-1β), cysteine aspartate-specific protease-3 (caspase-3), and 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels in the kidney and liver tissues and by increasing liver p53 and kidney interleukin-6 (IL-6) expressions. In other words, HSP administration reduced apoptosis, oxidative stress, inflammation, and oxidative DNA damage significantly in SA-induced kidney and liver tissues depending on dose. In this study, it was seen that HSP showed a protective effect against SA-induced kidney and liver toxicity.

Ellagic acid (EA) is a phenolic constituent in certain fruits and nuts with wide range of biological activities, including potent antioxidant, antidiabetic, anti-inflammatory, anticancer and antimutagen properties. The aim of this study was to evaluate the effect of EA on sodium arsenic (SA)-induced cardio- and hematotoxicity in rats. Animals were divided into five groups. The first group was used as control. Group 2 was orally treated with sodium arsenite (SA, 10 mg/kg) for 21 days. Group 3 was orally treated with EA (30 mg/kg) for 14 days. Groups 4 and 5 were orally treated with SA for 7 days prior to EA (10 and 30 mg/kg, respectively) treatment and continued up to 21 days simultaneous with SA administration. Various biochemical, histological and molecular biomarkers were assessed in blood and heart. The results indicate that SA-intoxicated rats display significantly higher levels of plasma cardiac markers (AST, CK-MB, LDH and cTnI) than normal control animals. Moreover, an increase in MDA and NO with depletion of GSH and activities of CAT, SOD and GPx occurred in the heart of rats treated with SA. Furthermore, SA-treated rats showed significantly lower WBC, RBC, HGB, HCT and PLT and significantly higher MCV and MCH. Administration of EA (30 mg/kg) resulted in a significant reversal of hematological and cardiac markers in arsenic-intoxicated rats. These biochemical disturbances were supported by histopathological observations of the heart. In conclusion, the results of this study suggest that EA treatment exerts a significant protective effect on SA-induced cardio- and hematotoxicity.

Chronic exposure to arsenic is associated with an increased risk of developing diabetes mellitus. Quinic acid (QA), a cyclic polyol compound with known antioxidant and anti-inflammatory properties, was evaluated for its protective effects against sodium arsenite (SA)-induced hyperglycemia and hepatotoxicity in mice. In this study, mice were divided into 6 groups: control, SA (10 mg/kg), QA (200 mg/kg), and three groups receiving SA + QA at doses of 50, 100, or 200 mg/kg. After 28 days of treatment, fasting blood glucose was measured, followed by a glucose tolerance test. On day 30, blood samples were collected for analysis of serum liver enzymes, triglycerides, and cholesterol. Hepatic oxidative stress markers, inflammatory markers, glucagon-like peptide-1 levels, and serum levels of gastric inhibitory polypeptide and insulin were also measured. Hepatic glucose transporter protein 2 (GLUT2) expression was assessed by Western blot. Histological analysis of liver and pancreatic tissues was also performed. Arsenic exposure resulted in impaired glucose tolerance, oxidative stress, inflammation, and liver injury. Treatment with QA significantly reduced these effects, restored antioxidant defenses, reduced inflammatory responses, and improved glycemic control. Western blot analysis showed that GLUT2 protein expression was decreased in the SA group, whereas QA increased hepatic GLUT2 expression in a dose-dependent manner.

Arsenic is a groundwater pollutant and can cause various cardiovascular disorders in the exposed population. The aim of the present study was to assess whether subchronic arsenic exposure through drinking water can induce vascular dysfunction associated with alteration in plasma electrolytes and lipid profile. Rats were exposed to arsenic as 25, 50, and 100 ppm of sodium arsenite through drinking water for 90 consecutive days. On the 91st day, rats were sacrificed and blood was collected. Lipid profile and the levels of electrolytes (sodium, potassium, and chloride) were assessed in plasma. Arsenic reduced high-density lipoprotein cholesterol (HDL-C) and HDL-C/LDL-C ratio, but increased the levels of triglycerides, total cholesterol, low-density lipoprotein cholesterol (LDL-C), and electrolytes. The results suggest that the arsenic-mediated dyslipidemia and electrolyte retention could be important mechanisms in the arsenic-induced vascular disorder.

Experimental verification of impairment to cognitive abilities and cognitive dysfunction resulting from inorganic arsenic (iAs) exposure in children and adults is challenging. This study aimed to elucidate the effects of arsenite (iAs III ; 1, 10 and 20 μM) or monomethylarsonous acid (MMA III ; 0.1, 1 and 2 μM) exposure on arsenic metabolism and tight junction (TJ) function in the blood–brain barrier (BBB) using a rat in vitro -BBB model. The results showed that a small percentage (~15%) of iAs III was oxidized or methylated within the BBB, suggesting the persistence of toxicity as iAs III . Approximately 65% of MMA III was converted to low-toxicity monomethylarsonic acid and dimethylarsenic acid via oxidation and methylation. Therefore, it is estimated that MMA III causes TJ injury to the BBB at approximately 35% of the unconverted level. TJ injury of BBB after iAs III or MMA III exposure could be significantly assessed from decreased expression of claudin-5 and decreased transepithelial electrical resistance values. TJ injury in BBB was found to be significantly affected by MMA III than iAs III . Relatedly, the penetration rate in the BBB by 24 h of exposure was higher for MMA III (53.1% ± 2.72%) than for iAs III (43.3% ± 0.71%) (p < 0.01). Exposure to iAs III or MMA III induced an antioxidant stress response, with concentration-dependent increases in the expression of nuclear factor-erythroid 2-related factor 2 in astrocytes and heme oxygenase-1 in a group of vascular endothelial cells and pericytes, respectively. This study found that TJ injury at the BBB is closely related to the chemical form and species of arsenic; we believe that elucidation of methylation in the brain is essential to verify the impairment of cognitive abilities and cognitive dysfunction caused by iAs exposure.

A large number of industries release their untreated wastes in the environment causing an increase in the concentration of toxic pollutants including heavy metal ions in ground and drinking water which is above the WHO limit. The presence of toxic pollutants in the industrial wastes pollutes our environment. Arsenic (As) is a ubiquitous toxic metalloid. Its amount varies in different parts on the earth, and its concentration is increasing in our environment day by day both by natural and anthropogenic activities. It is found in two forms; one is arsenate (As 5+ ) and other is arsenite (As 3+ ) and the latter is more toxic due to high mobility across the cell membrane. The long-term use of arsenic-containing water causes arsenicosis. High arsenic consumption, revealed by skin harms, color change, and spots on hands and feet, may cause skin cancer and affect lungs and kidneys. Hypertension, a state of high blood pressure, and lack of insulin which causes diabetes and many other disorders which relate to reproduction are the consequences of arsenic contamination. Several methods have been employed to decontaminate arsenic pollution, but the bioremediation by using biomass of bacteria, algae, fungi, and yeasts is the most compromising approach and has gained much attention from researchers in the last few decades. The microbial detoxification of arsenic can be achieved by reduction, oxidation, and methylation. High bioremediation potential and feasibility of the process make bacteria an impending foundation for green chemistry to exterminate arsenic in the environment.