Hematotoxicity and Genotoxicity of Mercuric Chloride Following Subchronic Exposure Through Drinking Water in Male Rats

Erythrocytes are a convenient model to understand the subsequent oxidative deterioration of biological macromolecules in metal toxicities. The present study examined the variation of hematoxic and genotoxic parameters following subchronic exposure of mercuric chloride via drinking water and their possible association with oxidative stress. Male rats were exposed to 50 ppm (HG1) and 100 ppm (HG2) of mercuric chloride daily for 90 days. A significant dose-dependent decrease was observed in red blood cell count, hemoglobin, hematocrit, and mean cell hemoglobin concentration in treated groups (HG1 and HG2) compared with controls. A significant dose-dependent increase was observed in lipid peroxidation; therefore, a significant variation was found in the antioxidant enzyme activities, such as superoxide dismutase, catalase, and glutathione peroxidase. Interestingly, mercuric chloride treatment showed a significant dose-dependent increase in frequency of total chromosomal aberration and in percentage of aberrant bone marrow metaphase of treated groups (p < 0.01). The oxidative stress induced by mercury treatment may be the major cause for chromosomal aberration as free radicals lead to DNA damage. These data will be useful in screening the antioxidant activities of natural products, which may be specific to the bone marrow tissue.     

Melatonin Ameliorates Neuropharmacological and Neurobiochemical Alterations Induced by Subchronic Exposure to Arsenic in Wistar Rats

Biological Trace Element Research - An experimental study was conducted in Wistar rats to characterize the arsenic (“As”)-induced alterations in neurobiochemistry in brain and its...     

Fenvalerate Exposure Alters Thyroid Hormone Status in Selenium- and/or Iodine-Deficient Rats

Considering the potential adverse effects of selenium and iodine deficiencies, and taking into account the widespread but often careless use of pyrethroid insecticides and their possible endocrine-disrupting effects, this study was undertaken to investigate the effects of fenvalerate on thyroid hormone parameters in both healthy and selenium- and/or iodine-deficient rats. Fenvalerate exposure had no effect on the TT4 levels of healthy controls but caused significant increases both in iodine deficiency (ID) and selenium plus iodine deficiency (ISeD), and a significant decrease in selenium deficiency (SeD). Dramatic increases in TT3 of all groups were observed by fenvalerate. Moreover, it caused insignificant decrease of thyroid stimulating hormone in healthy controls, no effect in SeD, and significant elevation in ID and ISeD. These results, thus, showed that the widely used pyrethroid insecticide fenvalerate has the potential to change significantly thyroid hormone parameters both in normal and deficiency states, and consequences of its thyroid status modifying effect might be of critical importance particularly in sensitive individuals and patients with thyroid dysfunction.     

Exposure to Low Level of Arsenic and Lead in Drinking Water from Antofagasta City Induces Gender Differences in Glucose Homeostasis in Rats

Populations chronically exposed to arsenic in drinking water often have increased prevalence of diabetes mellitus. The purpose of this study was to compare the glucose homeostasis of male and female rats exposed to low levels of heavy metals in drinking water. Treated groups were Sprague-Dawley male and female rats exposed to drinking water from Antofagasta city, with total arsenic of 30 ppb and lead of 53 ppb for 3 months; control groups were exposed to purified water by reverse osmosis. The two treated groups in both males and females showed arsenic and lead in the hair of rats. The δ-aminolevulinic acid dehydratase was used as a sensitive biomarker of arsenic toxicity and lead. The activity of δ-aminolevulinic acid dehydratase was reduced only in treated male rats, compared to the control group. Treated males showed a significantly sustained increase in blood glucose and plasma insulin levels during oral glucose tolerance test compared to control group. The oral glucose tolerance test and the homeostasis model assessment of insulin resistance demonstrated that male rats were insulin resistant, and females remained sensitive to insulin after treatment. The total cholesterol and LDL cholesterol increased in treated male rats vs. the control, and triglyceride increased in treated female rats vs. the control. The activity of intestinal Na+/glucose cotransporter in male rats increased compared to female rats, suggesting a significant increase in intestinal glucose absorption. The findings indicate that exposure to low levels of arsenic and lead in drinking water could cause gender differences in insulin resistance.     

Concentrations of Striatal Catecholamines in Rats Given Manganese Chloride Through Drinking Water

Abstract: Male albino rats were exposed to manganese through drinking solution containing MnCl₂·4H₂O (1 mg/ml) in water. The contents of catecholamines, homovanillic acid, manganese and the activity of monoamine oxidase (MAO) were measured in the corpus striatum at different time intervals up to a period of 360 days. The contents of tyrosine in the corpus striatum and serum were also estimated. Manganese treatment produced an initial increase in the contents of dopamine (DA), norepinephrine (NE), homovanillic acid (H VA) and tyrosine in the corpus striatum. This was followed by a period when concentrations were almost normal (dopamine from 120 to 240 days, norepinephrine at 180 and 240 days and homovanillic acid at 240 days after manganese administration). Thereafter the contents of these substrates declined significantly at 300 and 360 days of treatment. However, these alterations were not correlated with the concentrations of manganese in this region, which gradually increased up to 240 days, and thereafter remained constant until the termination of the experiment. The underlying biochemical mechanisms of manganese-induced sequential changes in the striatal contents of catecholamines have been discussed in relation to the development of psychiatric and neurological phases of manganese poisoning.     

Effects of Combined Exposure to Chronic High-Fat Diet and Arsenic on Thyroid Function and Lipid Profile in Male Mouse

The thyroid is one of the major endocrine glands that contribute to body and fat metabolism. The present study evaluated the effects of combined exposure to chronic high-fat diet (HFD) and arsenic on thyroid function and lipid profile. In this experimental study, 72 male Naval Medical Research Institute mice were divided into six groups and fed HFD or low-fat diet (LFD) while being exposed to 25 or 50 ppm of arsenic in drinking water for 20 weeks. After 24 h of the last experimental day, blood samples were collected for hormonal and biochemical measurements. The data indicated that exposure to HFD alone increased the levels of triiodothyronine (T3), thyroid-stimulating hormone (TSH), leptin, lipid profile, reactive oxygen species (ROS), and malondialdehyde (MDA) and decreased the levels of high-density lipoprotein, albumin, adiponectin, and glutathione sulfhydryl reductase (GSH), whereas exposure to arsenic alone decreased the levels of T3 and GSH and increased the levels of TSH, leptin, ROS, MDA, and T4/T3 ratio compared to those in the control LFD group. Furthermore, concomitant administration of HFD and arsenic decreased the lipid profile and levels of T4, albumin, total protein, T3, and GSH and increased the levels of TSH, adiponectin, leptin, ROS, MDA, and T4/T3 ratio compared to those in the control LFD or HFD group. In conclusion, combined exposure to HFD and arsenic induced hypothyroidism via reduction of thyroid hormones and enhancement of plasma TSH and T3 uptake levels concomitant with hypolipidemia, hyperleptinemia, hyperadiponectinemia, induction of oxidative stress, and reduction of GSH levels.     

Dietary Arsenic Intake in Taiwanese Districts with Elevated Arsenic in Drinking Water

Inorganic arsenic in dietary staples (i.e., yams and rice) may have substantially contributed to exposure and adverse health effects observed in an endemic Taiwanese population historically exposed to arsenic in drinking water. Observations of this population were used by the U.S. Environmental Protection Agency to derive toxicity values that form the basis for arsenic risk assessment and various regulations in the United States. However, data were previously insufficient to accurately estimate dietary intake. Rice and yam samples collected in 1993 and 1995 from Taiwanese districts with endemic arsenic were analyzed for total arsenic and for inorganic and organic mono and dimethylarsenic. The acid digestion techniques used in the analyses are among the best to preserve organic arsenic in the test sample. Furthermore, concurrent analyses of the proportion of inorganic arsenic in split samples of rice and yams collected in the 1995 investigation were in good agreement, despite using a different digestion method. These data support a likely mean dietary intake of 50?µg/day with a range of 15 to 211?µg/day. Consideration of dietary intake may result in a downward revision of the assumed potency of ingested arsenic as reflected in EPA's toxicity values.     

Importance of Arsenic Speciation in Populations Exposed to Arsenic in Drinking Water

Total arsenic in urine is often the principal means for assessing chronic exposure to arsenic-contaminated drinking water. This approach ignores many components of the human diet, especially fish and seafood that contain arsenic at significant concentrations. The toxicity differences between the inorganic forms and the dietary forms suggest both should be evaluated when attempting to assess risk from arsenic exposure. Urine biomonitoring for 53 participants was used to confirm reduction in arsenic exposure resulting from well water remediation removing inorganic arsenic from drinking water. Initially, only total arsenic urine assays were performed, but spikes in total arsenic urine concentrations were determined to be diet related and demonstrated the need for analytical methods that differentiate the arsenic species. A secondary analysis was added that quantified inorganic-related arsenic in urine and the dietary forms related to fish and seafood by subtraction from total arsenic. Significant differences were found between the inorganic arsenic component and the total arsenic measured in their urine. On average, approximately 76% of total arsenic in urine was attributed to fish and other organo-arsenic dietary sources, implying a potential significant overestimate of exposure, and demonstrating the need for differentiation of the inorganic-related arsenic from dietary arsenic.     

Evaluation of Toxic Risk Assessment of Arsenic in Male Subjects Through Drinking Water in Southern Sindh Pakistan

The arsenic (As) hazardous quotient was estimated based on concentration of As in drinking water and scalp hair of male subjects of two age groups (n = 360) consuming As contaminated water at different levels and non-contaminated drinking water. The total As concentrations in drinking water of less-exposed (LE) and high-exposed (HE) areas was found to be 3- to 30-fold higher than the permissible limit of the World Health Organization (2004) for drinking water, while the levels of As in drinking water of non-exposed (NE) areas was within the permissible limit. The levels of As in scalp hair samples of male subjects of two age groups belonging to NE, LE, and HE areas ranged from 0.01 to 0.27, 0.11–1.31, and 0.36–6.80 μg/g, respectively. A significant correlation between As contents of drinking water and As concentration in scalp hair was observed in sub-district Gambit (r = 0.825–0.852, p < 0.001) as compared to those subjects belonging to LE sub-district Thari Mirwah. A toxicity risk assessment provides a hazard quotient corresponding to <10 that indicates non-carcinogenic exposure risk of understudy areas.     

Effects of Subchronic Aluminum Exposure on the Reproductive Function in Female Rats

The aim of this study was to investigate the effects of aluminum (Al) exposure on the reproductive function in female rats. Forty female Wistar (5 weeks old) rats, weighing 110–120 g, were divided randomly into four groups. They were orally administrated with 0, 64.18, 128.36, and 256.72 mg aluminum chloride (AlCl₃) per kilogram body weight in drinking water for 120 days. Levels of Al, estrogen (E₂), progestogen (P), testosterone (T), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) in serum were measured at the end of experiment. The results showed that levels of E₂, P, FSH, and LH were significantly lower and Al concentration was significantly higher in all three Al-treated groups than those in the control group (GC). The level of T was significantly higher in the low- and medium-dose groups (GL and GM) (P < 0.05) but not in high-dose group (GH) compared with GC. The results suggest that the reproductive function of female rats is inhibited under long-term Al exposure in an Al dose-dependent manner.     

Longitudinal Exposure to Selected Pesticides in Drinking Water

The presence and temporal fluctuations of concentrations of insecticides and herbicides in natural waters has been well documented. Little, however, is known about exposure to pesticides through drinking water for the general population. Concentrations often pesticides, including 4,4′DDE and atrazine, were measured up to six times at equally spaced intervals over a 1-year period in drinking water of 80 randomly selected residences in Maryland. Atrazine was detected in 228 (57.9%) of the drinking water samples with a mean of 0.15?µg/L, with standard deviation 0.12?µg/L, median 0.17?µg/L, and range <0.037 to 0.46?µg/L. 4,4′DDE was found in 22 (5.6%) water samples; no other target analytes were detected. Concentrations of atrazine in drinking water were found to vary over a 12-month period with the greatest concentrations in the late summer and fall and the lowest in the early spring. Atrazine concentrations in drinking water were influenced more by differences in levels among residences than by time of year. Seven-day average exposures and exposures per unit body weight to atrazine in drinking water exhibited a similar temporal pattern. Among individuals, drinking water consumption rate was a more important determinant of atrazine exposure (µg/d) and exposure per unit body weight (µg/kg/d) than atrazine concentration in drinking water or body weight.     

Exposure to a Northern Contaminant Mixture (NCM) Alters Hepatic Energy and Lipid Metabolism Exacerbating Hepatic Steatosis in Obese JCR Rats

Non-alcoholic fatty liver disease (NAFLD), defined by the American Liver Society as the buildup of extra fat in liver cells that is not caused by alcohol, is the most common liver disease in North America. Obesity and type 2 diabetes are viewed as the major causes of NAFLD. Environmental contaminants have also been implicated in the development of NAFLD. Northern populations are exposed to a myriad of persistent organic pollutants including polychlorinated biphenyls, organochlorine pesticides, flame retardants, and toxic metals, while also affected by higher rates of obesity and alcohol abuse compared to the rest of Canada. In this study, we examined the impact of a mixture of 22 contaminants detected in Inuit blood on the development and progression of NAFLD in obese JCR rats with or without co-exposure to10% ethanol. Hepatosteatosis was found in obese rat liver, which was worsened by exposure to 10% ethanol. NCM treatment increased the number of macrovesicular lipid droplets, total lipid contents, portion of mono- and polyunsaturated fatty acids in the liver. This was complemented by an increase in hepatic total cholesterol and cholesterol ester levels which was associated with changes in the expression of genes and proteins involved in lipid metabolism and transport. In addition, NCM treatment increased cytochrome P450 2E1 protein expression and decreased ubiquinone pool, and mitochondrial ATP synthase subunit ATP5A and Complex IV activity. Despite the changes in mitochondrial physiology, hepatic ATP levels were maintained high in NCM-treated versus control rats. This was due to a decrease in ATP utilization and an increase in creatine kinase activity. Collectively, our results suggest that NCM treatment decreases hepatic cholesterol export, possibly also increases cholesterol uptake from circulation, and promotes lipid accumulation and alters ATP homeostasis which exacerbates the existing hepatic steatosis in genetically obese JCR rats with or without co-exposure to ethanol.     

Effects of Subchronic Aluminum Exposure on the Immune Function of Erythrocytes in Rats

This study assessed effects of aluminum (Al) exposure on the immune function of erythrocytes in rats. Forty male Wistar rats (5 weeks old) weighed 110–120 g were randomly allocated equally into four groups according to their weights and were orally exposed to 0, 64.18, 128.36, and 256.72 mg/kg body weight aluminum trichloride in drinking water for 120 days. Levels of erythrocytes C_3b receptor rate (RBC-C_3bRR), erythrocytes C_3b immune complex rosette rate (RBC-ICR), erythrocytes rosette forming enhancing rate (ERER) and erythrocytes rosette forming inhibitory rate (ERIR) were determined by the end of experiment. The three Al-treated groups had lower values of RBC-C_3bRR and ERER, and higher values of RBC-ICR and ERIR than those in control group. The levels of RBC-C_3bRR and ERER decreased, while the levels of RBC-ICR and ERIR increased with the increases of Al content in drinking water. The results suggest that the immune function of erythrocytes in rats is suppressed by Al exposure.     

Distribution and Speciation of Arsenic by Transplacental and Early Life Exposure to Inorganic Arsenic in Offspring Rats

The amount of arsenic compounds was determined in the liver and brain of pups and in breast milk in the pup's stomach in relation to the route of exposure: transplacental, breast milk, or drinking water. Forty-eight pregnant rats were randomly divided into four groups, each group was given free access to drinking water that contained 0, 10, 50, and 100 mg/L NaAsO₂ from gestation day 6 (GD 6) until postnatal day 42 (PND 42). Once pups were weaned, they started to drink the same arsenic-containing water as the dams. Contents of inorganic arsenic (iAs), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), and trimethylarsenic acid (TMA) in livers and brains of the pups on PND 0, 15, 28, and 42 and breast milk taken from the pup's stomach on PND 0 and 15 were detected using the hydride generation atomic absorption spectroscopy method. Concentrations of iAs, MMA, and DMA in the breast milk, the brain, and the liver of the pups increased with the concentration of arsenic in drinking water on PND 0, 15, 28, and 42. Compared to the liver or brain, breast milk had the lowest arsenic concentrations. There was a significant decrease in the levels of arsenic species on PND 15 compared to PND 0, 28, or 42. It was confirmed that arsenic species can pass through the placental barrier from dams to offspring and across the blood–brain barrier in the pups, and breast milk from dams exposed to arsenic in drinking water contains less arsenic than the liver and brain of pups.     

Effects of Subchronic Aluminum Exposure on Serum Concentrations of Iron and Iron-Associated Proteins in Rats

The purpose of the study was to investigate the effect of subchronic aluminum (Al) exposure on iron (Fe) homeostasis in rats. One hundred Wistar rats were divided into two groups. Experimental rats were given drinking water containing aluminum chloride (AlCl₃, 430 mg Al³⁺·L^?1), while control rats were given distilled water for up to 150 days. Ten rats were sacrificed in each group every 30 days. Mean corpuscular hemoglobin (MCH), and serum levels of Al, Fe, transferrin (TF), total iron binding capacity (TIBC), and soluble transferrin receptor (sTfR) were measured. Al-treated rats showed significantly decreased bodyweight and increased Al and Al/Fe levels during the experimental period. Fe levels and MCH were higher on day 150 in the experimental group than in the control group. TF content and TIBC were higher, whereas erythrocyte counts and sTfR content were lower in the experimental group than in the control group from days 90 and 60, respectively. Longer duration of Al administration increased the serum levels of Al, TF, Al/Fe, and TIBC and decreased sTfR. MCH and Fe levels decreased first, and then increased. The results indicate that chronic exposure to Al disturbed Fe homeostasis.     

Assessing Risk of Inorganic Arsenic in Drinking Water in the United States

Limitations of the current EPA risk assessment for inorganic arsenic in drinking water in the U.S. are discussed. An empirical approach is suggested that would sample survey the populations in regions with the highest arsenic levels in drinking water for signs of arsenicism, which has been much more prevalent and appeared much earlier in exposed populations than cancer (e.g., of the skin). Biomarkers of exposure, such as arsenic content in urine, nails, hair, and skin scales, may provide even earlier indications of subpopulations with excessive arsenic exposure and identify individuals at risk. Further study is needed to evaluate fully the potential for use of biomarkers, focusing on the accuracy and reliability of analytical methods, the utility of biomarkers as indicators of short-term and long-term exposure and as precursors to clinical signs of arsenicism, and the use of “normal” ranges of biomarkers for interpretation of field observations.     

Prenatal Morphine Exposure Differentially Alters Addictive and Emotional Behavior in Adolescent and Adult Rats in a Sex-Specific Manner

The effects of prenatal opioid exposure in adult animals has been widely studied, but little is known about the effects of prenatal opioid on adolescents. Most of the risk behaviors associated with drug abuse are initiated during adolescence. The developmental state of the adolescent brain makes it vulnerable to initiate drug use and susceptible to drug-induced brain changes. In this study, pregnant rats were subcutaneously injected with an increasing dose of morphine (5 mg/kg, 7 mg/kg, 10 mg/kg) for 9 days since the gestation day 11. The effects of prenatal morphine (PNM) on learning and memory, anxiety- and depressive- like behavior, morphine induced conditioned place preference (CPP) as well as locomotor sensitization were tested in both adolescent and adult rats. The results showed that: (1) PNM decreased anxiety-like behavior in both adolescent and adult female rats, but not males; (2) PNM decreased depressive-like behavior in adolescent but increased depressive -like behavior in adult females; (3) PNM increased low dose morphine induced locomotor sensitization in females; (4) PNM decreased tyrosine hydroxylase (TH) expression in the prefrontal cortex but decreased dopamine D1 receptor expression in the nucleus-accumbens (NAc) in female rats. These results suggested that PNM altered the emotional and addictive behavior mainly in female rats, with female rats being less anxiety and depressive during adolescence, but more depressive in adult, and more sensitive to low dose morphine induced locomotor activity sensitization, which might be mediated in part by the differential expression of the TH, dopamine D1 receptors in the female brain.

     

Changes in Serum Adiponectin in Mice Chronically Exposed to Inorganic Arsenic in Drinking Water

Cardiovascular disease and diabetes mellitus are prominent features of glucose and lipid metabolism disorders. Adiponectin is a key adipokine that is largely involved in glucose and lipid metabolism processes. A growing body of evidence suggests that chronic exposure to inorganic arsenic is associated with cardiovascular disease and diabetes mellitus. We hypothesized that arsenic exposure may increase the risk of cardiovascular disease and diabetes mellitus by affecting the level of adiponectin. In this study, we examined serum adiponectin levels, as well as serum levels of metabolic measures (including fasting blood glucose, insulin, total cholesterol, triglyceride, and high-density lipoprotein (HDL)-cholesterol) in C57BL/6 mice exposed to inorganic arsenic in drinking water (5 and 50 ppm NaAsO₂) for 18 weeks. Body mass and adiposity were monitored throughout the study. We found no significant changes in serum insulin and glucose levels in mice treated with arsenic for 18 weeks. However, arsenic exposure decreased serum levels of adiponectin, triglyceride, and HDL-cholesterol. Further, an inverse relationship was observed between urinary concentrations of total arsenic and serum levels of adiponectin. This study suggests that arsenic exposure could disturb the metabolism of lipids and increase the risk of cardiovascular disease by reducing the level of adiponectin.