Lithium Treatment Aggregates the Adverse Effects on Erythrocytes Subjected to Arsenic Exposure

The present study was designed to investigate the effects of lithium treatment on red blood cells which were given arsenic exposure. Long-term lithium therapy is being extensively used for the treatment of bipolar disorders. Arsenic is a group I carcinogen and a major toxic pollutant in drinking water that affects millions of people worldwide. Male SD rats were segregated into four groups, viz. normal control, lithium treated, arsenic treated, and lithium + arsenic treated. Lithium was supplemented as lithium carbonate at a dose level of 1.1 g/kg diet for a period of 8 weeks. Arsenic was given in the form of sodium arsenite at a dose level of 100 ppm in drinking water, ad libitum, for the same period. Lysates of red blood cells were used to investigate the effects of lithium and arsenic treatments on anti-oxidant enzymes, reduced glutathione (GSH), and lipid peroxidation (LPO) levels. Various hematological parameters, activities of Na⁺ K⁺ ATPase and delta-aminolevulinic acid dehydratase (δ-ALAD) were also assessed. A significant reduction was observed in the activities of antioxidant enzymes, GSH levels, total erythrocyte counts, Na⁺ K⁺ ATPase, and ALAD enzyme activities in lysates of red blood cells when exposed either to lithium or arsenic. In addition, a significant increase in the levels of malondialdehyde (MDA), lymphocytes, neutrophils, and total leukocytes was also observed following lithium as well as arsenic treatments. However, when arsenic-treated rats were subjected to lithium treatment, a pronounced alteration was noticed in all the above parameters. Therefore, we conclude that lithium supplementation to the arsenic-treated rats enhances the adverse effects on red blood cells and therefore use of lithium may not be medicated to patients who are vulnerable to arsenic exposure through drinking water. It can also be inferred that adverse effects of lithium therapy may get aggravated in patients thriving in the arsenic-contaminated area.

     

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.     

Exposure to Malondialdehyde Induces an Early Redox Unbalance Preceding Membrane Toxicity in Human Erythrocytes

This work investigated the oxidative injury to human red blood cells (RBCs) by the exposure to exogenous malondialdehyde (MDA), in a physiological environment. When a 10% RBC suspension was incubated in autologous plasma, in the presence of 50 &#117 &#119 M MDA, 30% of MDA entered into the cells. A time-course study showed that MDA caused early (30-120 &#117 min) and delayed (3-18 &#117 h) effects. MDA caused a fast depletion of reduced glutathione, and loss of the glucose-6-phosphate dehydrogenase activity, followed by a decrease of HbO 2 . Accumulation of methemoglobin, and formation of small amounts of hemichrome were later evident. Also, an HbO 2 -derived fluorescent product was measured in the membrane. The redox unbalance was followed by structural and functional damage to the membrane, evident as the formation of conjugated diene lipid hydroperoxides, concurrent with a sharp accumulation of MDA, consumption of membrane vitamin E, and egress of K + ions. SDS--PAGE of membrane proteins showed formation of high molecular weight aggregates. In spite of the marked oxidative alterations, the incubation plasma prevented a substantial hemolysis, even after a 18 &#117 h incubation. On the contrary, the exposure of RBCs to 50 &#117 &#119 M MDA in glucose-containing phosphate saline buffer, resulted in a 16% hemolysis within 6 &#117 h. These results indicate that the exposure to MDA causes a rapid intracellular oxidative stress and potentiates oxidative cascades on RBCs, resulting in their dysfunction.     

Probabilistic Analysis of Human Health Risks Associated with Background Concentrations of Inorganic Arsenic: Use of a Margin of Exposure Approach

Substantial evidence exists from epidemiological and mechanistic studies supporting a sublinear or threshold dose–response relationship for the carcinogenicity of ingested arsenic; nonetheless, current regulatory agency evaluations have quantified arsenic risks using default, generic risk assessment procedures that assume a linear, no-threshold dose–response relationship. The resulting slope factors predict risks from U.S. background arsenic exposures that exceed certain regulatory levels of concern, an outcome that presents challenges for risk communication and risk management decisions. To better reflect the available scientific evidence, this article presents the results of a Margin of Exposure (MOE) analysis to characterize risks associated with typical and high-end background exposures of the U.S. population to arsenic from food, water, and soil. MOE values were calculated by comparing a no-observable-adverse-effect-level (NOAEL) derived from the epidemiological literature with exposure estimates generated using a probabilistic (Monte Carlo) model. The plausibility and conservative nature of the exposure and risk estimates evaluated in this analysis are supported by sensitivity and uncertainty analyses and by comparing predicted urinary arsenic concentrations with empirical data. Using the more scientifically supported MOE approach, the analysis presented in this article indicates that typical and high-end background exposures to inorganic arsenic in U.S. populations do not present elevated risks of carcinogenicity.     

Human Exposure to Arsenic,Cadmium, Mercury,and Lead from Foods in Catalonia,Spain: Temporal Trend

The main purpose of this study was to establish the temporal trend in the daily dietary intake of arsenic (As), cadmium (Cd), mercury (Hg), and lead (Pb) by the population of Catalonia, Spain. Concentrations of these elements were determined in samples of a number of food items widely consumed in that country. The dietary intake of As, Cd, Hg, and Pb was then estimated for various age–gender groups of population: children, adolescents, adults, and seniors. In the present study, the dietary intakes of As, inorganic As, Cd, Hg, methylmercury, and Pb were 328.37, 16.22, 19.47, 11.39, 10.25, and 101.47 μg/day, respectively, while in a previous (2006) survey, the dietary intakes of As, inorganic As, Cd, Hg, methylmercury, and Pb were 261.01, 33.17, 9.80, 12.61, 11.35, and 45.13 μg/day, respectively. The estimated intakes of Cd, Hg, and Pb are still notably lower than the respective PTWIs, while that of inorganic As is also lower than its BMDL₀₁. In summary, the results of this study indicate that, currently, the dietary intakes of As, Cd, Hg, and Pb should not mean additional health risks for the consumers.     

Role of Reactive Oxygen Species and Glutathione in Inorganic Mercury-Induced Injury in Human Glioma Cells

The present study was undertaken to examine the role of reactive oxygen species (ROS) and glutathione (GSH) in glia cells using human glioma cell line A172 cells. HgCl₂ caused the loss of cell viability in a dose-dependent manner. HgCl₂-induced loss of cell viability was not affected by H₂O₂ scavengers catalase and pyruvate, a superoxide scavenger superoxide dismutase, a peroxynitrite scavenger uric acid, and an inhibitor of nitric oxide N^G-nitro-arginine Methyl ester. HgCl₂ did not cause changes in DCF fluorescence, an H₂O₂-sensitive fluorescent dye. The loss of cell viability was significantly prevented by the hydroxyl radical scavengers dimethylthiourea and thiourea, but it was not affected by antioxidants DPPD and Trlox. HgCl₂-induced loss of cell viability was accompanied by a significant reduction in GSH content. The GSH depletion was almost completely prevented by thiols dithiothreitol and GSH, whereas the loss of viability was partially prevented by these agents. Incubation of cells with 0.2 mM buthionine sulfoximine for 24 hr, a selective inhibitor of -glutamylcysteine synthetase, resulted in 56% reduction in GSH content without any change in cell viability. HgCl² resulted in 34% reduction in GSH content, which was accompanied by 59% loss of cell viability. These results suggest that HgCl₂-induced cell death is not associated with generation of H₂O₂ and ROS-induced lipid peroxidation. In addition, these data suggest that the depletion of endogenous GSH itself may not play a critical role in the HgCl₂-induced cytotoxicity in human glioma cells.     

Effects of Melatonin on Carbonic Anhydrase from Human Erythrocytes In Vitro and from Rat Erythrocytes In Vivo

The in vitro effects of melatonin (N-acetyl-5-methoxytryptamine) on human carbonic anhydrase isozymes (HCA-I and HCA-II) from human erythrocytes and in vivo effects on rat erythrocytes carbonic anhydrase (CA) were determined. Human erythrocyte carbonic anhydrase isozymes were purified by haemolysate preparation and Sepharose-4B-L tyrosine-sulfanilamide affinity gel chromatography. The HCA-I enzyme, having a specific activity of 7337.5?EU/mg protein, was purified 843-fold with a yield of 60% and the HCA-II enzyme, having a specific activity of 17067?EU/mg protein, was purified 1962-fold with a yield of 22.7%. For in vitro experiments, the enzyme activity was minimal at 2×10-4?M melatonin concentration and increased above this concentration. Ten mg?kg-1 melatonin was administered intraperitoneally and showed a stimulatory effect on the enzyme. Time-dependent in vivo studies were conducted for melatonin in Sprague–Dawley type rats. It was found that CA activity in the rat erythrocytes was decreased by the melatonin after 1 and 3 hours to 2500±500.0 and 1875±239.4 respectively which were statistically significant (p<0.05) differences to the control (2660±235.8). However, CA activity was restored to its normal level after 6?h (2666±235.7) (p>0.05) probably due to metabolism of the melatonin. The findings indicate that melatonin may be pharmacologically useful in some diseases.     

红细胞羰基毒化及谷胱甘肽的保护作用

探索丙二醛（MDA）对红细胞的羰基毒化过程,以及谷胱甘肽（GSH）的拮抗作用．采用血液粘度测量、扫描电镜观察、羰基化蛋白含量测定以及荧光偏振度检测等方法,从红细胞表观粘度、红细胞形态、红细胞膜上羰基化蛋白含量以及红细胞膜脂流动性4个指标上进行研究．MDA导致的羰基应激造成红细胞损伤和血液粘度增加,而GSH可阻止羰基应激或还原羰．氨反应产物,且具有浓度依赖性．揭示了羰基应激可能是血瘀证的关键生化原因之一．为抗应激、抗衰老提供了理论和实验的重要依据．     

Thymus-independent Step in the Immune Response to Sheep Erythrocytes

THE nature of the T and B cell interaction in the response to erythrocyte antigens¹ has been an area of intense interest recently. Perhaps because of the influences of molecular biology, there has been a tendency to invoke specific mechanisms such as informational RNA and thymus specific immunoglobulins as mediators of this synergism. But once it was demonstrated that antigen specific receptors of immunoglobulin nature were on the surface of immune competent cells², it was possible to approach the problem more simply; that is from the viewpoint of control of protein synthesis and/or release of proteins from the cell surface. This communication outlines recent evidence concerning the role of non-specific mitogens in the control of antibody precursor (B cells) and antibody secreting cells.     

Hxt-Carrier-Mediated Glucose Efflux upon Exposure of Saccharomyces cerevisiae to Excess Maltose

When wild-type Saccharomyces cerevisiae strains pregrown in maltose-limited chemostat cultures were exposed to excess maltose, release of glucose into the external medium was observed. Control experiments confirmed that glucose release was not caused by cell lysis or extracellular maltose hydrolysis. To test the hypothesis that glucose efflux involved plasma membrane glucose transporters, experiments were performed with an S. cerevisiae strain in which all members of the hexose transporter (HXT) gene family had been eliminated and with an isogenic reference strain. Glucose efflux was virtually eliminated in the hexose-transport-deficient strain. This constitutes experimental proof that Hxt transporters facilitate export of glucose from S. cerevisiae cells. After exposure of the hexose-transport-deficient strain to excess maltose, an increase in the intracellular glucose level was observed, while the concentrations of glucose 6-phosphate and ATP remained relatively low. These results demonstrate that glucose efflux can occur as a result of uncoordinated expression of the initial steps of maltose metabolism and the subsequent reactions in glucose dissimilation. This is a relevant phenomenon for selection of maltose-constitutive strains for baking and brewing.     

Health Risk Assessment for Human Exposure to Trace Metals and Arsenic via Consumption of Hen Egg Collected from Largest Poultry Industry in Iran

Biological Trace Element Research - The relative contribution of foodstuffs to intake of heavy metal is still equivocal, and thus, available data are rare. Here, the concentration of ten heavy...     

Response of Mouse T and B Lymphocytes to Sheep Erythrocytes

THE primary immune response of mice to sheep red blood cells (SRBC) involves two types of lymphocytes: the antibody-forming cell series, whose precursors are found in bone marrow (B cells) and cooperating or “helper” cells of uncertain function whose precursors are found in the thymus (T cells)¹. Within 24 h of an intravenous injection of SRBC, an increase of haemolytic antibody plaque-forming cells (p.f.c.) occurs in the spleen, reaching a peak 5 days later. Part, but not all, of this increase is due to division among the B cells². T cells in the spleen also undergo a wave of mitosis, detectable from the second to the fifth day³.     

人脑及红细胞膜乙酰胆碱酯酶的芳基酰胺酶活性

采用联合亲和层析法从人小脑及红细胞膜中纯化了ＡＣｈＥ,纯化的人脑及红细胞ＡＣｈＥ在ＳＤＳ－ＰＡＧＥ上呈一主带,分子量约为６６０００。人脑ＡＣｈＥ制备酯酶与酰胺酶比活性分别为１２９９与１４３Ｕ／ｍｇ,人红细胞ＡＣｈＥ制备分别为４５８４与７４７Ｕ／ｍｇ。人脑及红细胞ＡＣｈＥ制备的酯酶与酰胺酶活性最适ｐＨ较接近,在ｐＨ７．５－８．０之间,酯酶活性底物ＡＴＣｈ对其芳基酰胺酶活性有抑制作用。ＩＣ_（５０）分别为１０．２×１０~（－３）及３×１０~（－３）ｍｏｌ／Ｌ。梭曼对其酯酶及酰胺酶活性均有明显抑制作用,说明二者均需活性中心丝氨酸参与。     

The Large Scale Purification of Ubiquitin from Human Erythrocytes

A simple, reproducible method for the large-scale purification of active ubiquitin from human erythrocytes is described. Erythrocytes contain 100 μg free ubiquitin per cc of packed cells, of which 44% can be recovered in homogeneous form by a combination of heat treatment, ammonium sulfate fractionation, and ion exchange chromatography.     

人红细胞NADH－细胞色素b5还原酶的分离纯化与鉴定

 人红细胞ＮＡＤＨ－细胞色素ｂ５还原酶的分离纯化与鉴定黄长晖,朱忠勇,唐玉钗（南京军区福州总院全军医学检验中心实验科,福州３５０００１）ＮＡＤＨ细胞色素ｂ５还原酶（Ｃｙｔｂ５Ｒ,Ｅ．Ｃ．１．６．２．２．）是红细胞内催化高铁血红蛋白还原为血红蛋白的关键酶...