Administration Of Arsenic Research Articles

Protective effects of methanolic extract of Andrographis paniculata (Burm.f.) Nees leaves against arsenic-induced damage in rats

BackgroundMedicinal plants are natural sources of antioxidants effective in the treatment of oxidative stress-mediated diseases. This study aims to evaluate the hepato-renal protective efficacy of Andrographis paniculata leaves methanolic extract in arsenic-induced oxidative stress. Animals were divided into four groups of six animals per group. The rats in groups 1 and 2 received normal saline, while rats in groups 3 and 4 received 200 mg/kg body weight of A. paniculata or ascorbic acid per day, respectively, for 7 days orally. The rats in groups 2, 3, and 4 received a single dose of arsenic at 10 mg/kg body weight intraperitoneally on day 7, and 24 h later, rats in all the groups were killed and the blood, liver, and kidney samples were collected for biochemical/histological studies.ResultsAdministration of arsenic to rats induced a significant increase in the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), cholesterol, urea, creatinine, and triglycerides in the plasma, while it decreased superoxide dismutase (SOD), glutathione (GSH) and catalase (CAT) activities in the liver and kidney. It also significantly reduced the levels of white blood cells (WBC), red blood cells (RBC), platelet (PLT), and lymphocytes (LYM) in the blood. However, the levels of AST, ALT, cholesterol, urea, creatinine, and triglycerides in the plasma of groups of rats that received A. paniculata extract before administration of arsenic were decreased, while their SOD, GSH, and CAT levels were elevated in the liver and kidney. The values of their WBC, RBC, PLT, and LYM were also significantly increased when compared to the arsenic group rats. Histological observations showed varying degrees of liver damage in the arsenic group rats, while the histoarchitecture of the liver of rats that received A. paniculata extract were significantly improved.ConclusionsThis study demonstrated that A. paniculata extract ameliorates arsenic-induced hepato-renal toxicity and could be exploited in the management of toxicity effects associated with the arsenic.

Polyphenolics with Strong Antioxidant Activity from Acacia nilotica Ameliorate Some Biochemical Signs of Arsenic-Induced Neurotoxicity and Oxidative Stress in Mice.

Neurotoxicity is a serious health problem of patients chronically exposed to arsenic. There is no specific treatment of this problem. Oxidative stress has been implicated in the pathological process of neurotoxicity. Polyphenolics have proven antioxidant activity, thereby offering protection against oxidative stress. In this study, we have isolated the polyphenolics from Acacia nilotica and investigated its effect against arsenic-induced neurotoxicity and oxidative stress in mice. Acacia nilotica polyphenolics prepared from column chromatography of the crude methanol extract using diaion resin contained a phenolic content of 452.185 ± 7.879 mg gallic acid equivalent/gm of sample and flavonoid content of 200.075 ± 0.755 mg catechin equivalent/gm of sample. The polyphenolics exhibited potent antioxidant activity with respect to free radical scavenging ability, total antioxidant activity and inhibition of lipid peroxidation. Administration of arsenic in mice showed a reduction of acetylcholinesterase activity in the brain which was counteracted by Acacia nilotica polyphenolics. Similarly, elevation of lipid peroxidation and depletion of glutathione in the brain of mice was effectively restored to normal level by Acacia nilotica polyphenolics. Gallic acid methyl ester, catechin and catechin-7-gallate were identified in the polyphenolics as the major active compounds. These results suggest that Acacia nilotica polyphenolics due to its strong antioxidant potential might be effective in the management of arsenic induced neurotoxicity.

Arsenic Biotransformation: It is a complex process

Arsenic Biotransformation: It is a complex process

M.D. Lyon. Specific treatment for epilepsy. Doctor. Gas. 1910, No. 49.

The author recommends, in the treatment of epilepsy, the subcutaneous administration of Cerebrin in combination with the subcutaneous administration of arsenic (Natr. Cacodyl).

Selenium (Se) as well as mercury (Hg) may influence the methylation and toxicity of inorganic arsenic, but further research is needed with combination of Inorg-arsenic, Se, and Hg

Selenium (Se) as well as mercury (Hg) may influence the methylation and toxicity of inorganic arsenic, but further research is needed with combination of Inorg-arsenic, Se, and Hg

Regulation of transgelin and GST-pi proteins in the tissues of hamsters exposed to sodium arsenite

Regulation of transgelin and GST-pi proteins in the tissues of hamsters exposed to sodium arsenite

Antioxidant effects of Emblica officinalis and Zingiber officinalis on arsenic and lead induced toxicity on Albino rats

It is of interest to document the effect of Emblica officinalis (E. officinalis) and Zingiber officinalae (Z. officinalae) leaf extract on reactive oxygen species, antioxidant potential changes in arsenic and lead-induced toxicity in male rats. We used 8 groups of adult male Wistar rats with 1 control group for this study. The animals were divided into Group I: Control and Group II: Lead and sodium arsenite induced rats (animals were induced for metal toxicity by the combined administration of arsenic (13.8 mg/kg body weight) and lead (116.4 mg/kg body weight). These doses were administered by gastric intubation during 14 consecutive days using known standard procedures. Arsenic and lead induced rats treated with ethanolic extract of Emblica officinalis (60 mg/kg body weight/day, orally for 45 days) are group III rats.Group IV animals are arsenic and lead induced rats treated orally with ethanolic extracts of E. officinalis (120 mg/kg body weight/day for 45 days). Group V animals are arsenic and lead induced rats treated orally with ethanolic extracts of Z. officinalae (60 mg/kg body weight/day for 45 days). Group VI animals are arsenic and lead induced rats orally treated with ethanolic extracts of Zingiber officinalis (120 mg/kg body weight/day for 45 days). Group VII animals are arsenic and lead induced rats treated orally with ethanolic extracts of E. officinalis and Z. officinalae (60 + 60 mg/kg body weight/day for 45 days). Group VIII animals are arsenic and lead induced rats treated orally with ethanolic extracts of E. officinalis and Z. officinalae (120 + 120 mg/kg body weight/day, orally for 45 days). Normal Control animals were treated orally with ethanolic extracts of E. officinalis (120mg/kg body weight) + Z. officinalae (120mg/kg body weight) for 45 days. The control and experimental animals were then subjected to analysis for oxidative stress markers such as H2O2, *OH, and lipid peroxidation (LPO), antioxidant enzymes in addition to liver and kidney function markers. Results: Arsenic and lead induced rats showed a significant increase in the levels of reactive oxygen species (H2O2, OH* and LPO) with concomitant alterations in the renal and liver tissues. However, enzymic and non-enzymic antioxidant levels were decreased. Nevertheless, an oral effective dose of E. officinalis and Z. officinalae (120 + 120 mg/kg body weight/day increased the antioxidant enzymes and retrieved the altered levels of ROS and LPO that were induced by arsenic and lead. Thus, we show that E. officinalis and Z. officinalae leaf extract exhibits nephroprotective and hepatoprotective role through the restoration of reactive oxygen species and antioxidant enzymes in the kidney and liver tissue of Arsenic and Lead-induced nephrotoxicity and hepatotoxicity in rats. Hence, E. officinalis and Z. officinalae leaf extract are potential therapeutic options for the treatment of metal toxicity-induced kidney and liver diseases.

Antioxidant effects of Emblica officinalis and Zingiber officinalis on arsenic and lead induced toxicity on Albino rats.

It is of interest to document the effect of Emblica officinalis (E. officinalis) and Zingiber officinalae (Z. officinalae) leaf extract on reactive oxygen species, antioxidant potential changes in arsenic and lead-induced toxicity in male rats. We used 8 groups of adult male Wistar rats with 1 control group for this study. The animals were divided into Group I: Control and Group II: Lead and sodium arsenite induced rats (animals were induced for metal toxicity by the combined administration of arsenic (13.8 mg/ kg body weight) and lead (116.4 mg/kg body weight). These doses were administered by gastric intubation during 14 consecutive days using known standard procedures. Arsenic and lead induced rats treated with ethanolic extract of Emblica officinalis (60 mg/kg body weight/day, orally for 45 days) are group III rats. Group IV animals are arsenic and lead induced rats treated orally with ethanolic extracts of E. officinalis (120 mg/kg body weight/day for 45 days). Group V animals are arsenic and lead induced rats treated orally with ethanolic extracts of Z. officinalae (60 mg/kg body weight/day for 45 days). Group VI animals are arsenic and lead induced rats orally treated with ethanolic extracts of Zingiber officinalis (120 mg/kg body weight/day for 45 days). Group VII animals are arsenic and lead induced rats treated orally with ethanolic extracts of E. officinalis and Z. officinalae (60 + 60 mg/kg body weight/day for 45 days). Group VIII animals are arsenic and lead induced rats treated orally with ethanolic extracts of E. officinalis and Z. officinalae (120 + 120 mg/kg body weight/day, orally for 45 days). Normal Control animals were treated orally with ethanolic extracts of E. officinalis (120mg/kg body weight) + Z. officinalae (120mg/kg body weight) for 45 days. The control and experimental animals were then subjected to analysis for oxidative stress markers such as H2O2, *OH, and lipid peroxidation (LPO), antioxidant enzymes in addition to liver and kidney function markers. Results: Arsenic and lead induced rats showed a significant increase in the levels of reactive oxygen species (H2O2, OH* and LPO) with concomitant alterations in the renal and liver tissues. However, enzymic and non-enzymic antioxidant levels were decreased. Nevertheless, an oral effective dose of E. officinalis and Z. officinalae (120 + 120 mg/kg body weight/day increased the antioxidant enzymes and retrieved the altered levels of ROS and LPO that were induced by arsenic and lead. Thus, we show that E. officinalis and Z. officinalae leaf extract exhibits nephroprotective and hepatoprotective role through the restoration of reactive oxygen species and antioxidant enzymes in the kidney and liver tissue of Arsenic and Lead-induced nephrotoxicity and hepatotoxicity in rats. Hence, E. officinalis and Z. officinalae leaf extract are potential therapeutic options for the treatment of metal toxicity-induced kidney and liver diseases.

Toxicological effects of the concurrent administration of cadmium and arsenic through the food chain on the liver and kidney of rats

BackgroundOur environment is filled with a mixture of toxic elements.ObjectivesThis study seeks to assess the effects of exposure to cadmium and arsenic through the food chain on the liver and kidney of rats.MethodologyAdult male albino rats were exposed to experimental feed of which the protein composition was made of fish exposed to cadmium and arsenic for 1 month at a concentration of 0.4 mg cadmium or/and arsenic/100 ml water for 1 and 3 months. Samples of feed and tissue were assayed for cadmium and arsenic load. Tissue homogenates were used for biochemical analysis and the estimation of the expression levels of mRNA of Bax and Bcl2 genes in the liver and kidney of rats were carried out. Samples of tissues were also used for histological analysis.ResultsResults show a greater accumulation of metals in the liver than kidney of rats after the 1-month exposure of which the trend changed after the 3-month exposure. Alterations in enzymatic activities and levels of MDA and GSH were also recorded. Significant (P < 0.05) alterations in the level of mRNA expression of the Bax and Bcl2 genes were observed in all groups compared to the control for both duration of treatment. Treatment-related lesions were also observed for the various groups from the histopathological analysis.ConclusionThe cadmium-contaminated diet was found to be more toxic to the kidney while the arsenic-contaminated diet was found to be toxic to the liver. In addition, the present study has shown that the toxicity of a mixture of As + Cd cannot be predicted from the toxic mechanisms of the single components.

Toxic Effects of Chronic Exposure to High-Fat Diet and Arsenic on the Reproductive System of the Male Mouse

Objective: Obesity is associated with reproductive disorders. Arsenic disrupts male reproduction by direct effects on the male gonads or androgens secretion. So, the present study was conducted to evaluate the toxic effects of chronic concomitant administration of high-fat diet (HF) and arsenic on the reproductive system of the male mouse. Materials and methods: In this experimental study, 72 adult male mice were randomly divided into 6 groups: low-fat diet (LF0), LF+arsenic 25 ppm, LF+arsenic 50ppm, HF0, HF+arsenic 25 ppm and, HF+arsenic 50 ppm. 24 hours after the last experimental day, plasma samples, the cauda of epididymis and testis were prepared and removed for hormonal, sperm count and histopathological assessments. Results: Testis weight and volume increased in HF0 than other groups except for LF0. Plasma LH and testosterone levels decreased in LF50, HF0, HF25, and HF50 compared to LF0. A similar effect was observed in plasma FSH levels of HF0, HF25 and HF50 groups compared with LF0. Plasma level of estradiol increased in LF50 versus to other groups. Testosterone to estradiol ratio and sperm count decreased in all groups compared to LF0. Reduced interstitial cells and large numbers of vacuoles were observed in germinal epithelium of HF0 group, that these changes were more intense in both concentrations of arsenic-treated mice. Conclusion: Present study indicated that chronic exposure to HF and arsenic-induced hypogonadotropic hypogonadism concomitant with sperm count reduction and testicular damage.

Brown adipose tissue metabolism in arsenic environmental health and obesity

Arsenic is an element that occurs naturally in the environment. Humans are likely to be exposed to higher amount of arsenic through arsenic contaminated drinking water and consuming foods including fruits and vegetables, and the arsenic can accumulate in the human body at high concentrations. Previous research has shown that arsenic induces oxidative stress linked to metabolic diseases such as obesity and diabetes. In mice, arsenic exposure during embryonic development is linked to an early puberty and adult obesity. Recent findings of brown adipocytes, capable of dissipating energy as heat, in adult humans have promised new hope for obesity treatment and prevention. Therefore, understanding the pathophysiological role of brown adipocytes and uncoupling protein 1 (UCP1) regulation in thermogenesis can provide effective strategies against obesity. Here, we investigated the effects of arsenic on differentiation, mitochondrial respiration and thermogenesis in immortalized murine brown adipocytes. We observed that arsenic significantly reduced brown adipocyte differentiation in dose dependent manner. Arsenic suppressed mitochondrial respiration and biogenesis, leading to attenuated brown adipocytes specific thermogenesis functions including UCP1 in immortalized murine brown adipocytes. In mice studies, we confirmed the heavy arsenic accumulation in brown adipose tissue (BAT) and the suppression of gene expression levels of mitochondria specific markers after the oral administration of arsenic into mice at dose of 10 mg/kg/day for 9 days. Arsenic significantly suppressed the BAT thermogenesis marker UCP1 when exposed to cold temperature for 24 hr at the last day of oral gavage. These results reveal the underlying mechanism of how arsenic aggravates metabolic diseases such as obesity by suppressing brown adipocyte differentiation, mitochondria function and thermogenesis, which can be utilized for development of arsenic‐specific inhibitor drugs protecting essential physiological functions of BAT in humans.Support or Funding InformationThis work was supported by University of Nebraska‐Lincoln ARD/ORED/BIOC grants, Layman award, Nebraska Tobacco Settlement‐Biomedical research enhancement funds, and Nebraska Center for thePrevention of Obesity Diseases (NPOD) seed grant from NIH (P20GM104320) to S.R.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Potentiating effect of imidacloprid on arsenic-induced testicular toxicity in Wistar rats

BackgroundIt is an established fact that humans and animals are exposed to more than one chemical concurrently from various sources such as food, air and water. In the past, much emphasis was laid on evaluating the toxic effects of a single chemical. Nowadays an increased attention is being paid to the interaction of xenobiotics with one another. Therefore, a study was aimed to evaluate the potentiating effect of imidacloprid (IMI) on arsenic-induced testicular toxicity in rats.MethodsAdult male Wistar rats randomly divided into eight groups with six in each were subjected to daily oral administrations for 28 days. Group I served as control, group II received IMI at the dose rate of 16.9 mg/kg body weight, group III, IV and V received arsenic at the dose rate of 50, 100 and 150 ppb in drinking water whereas group VI, VII and VIII received both arsenic and IMI.ResultsRepeated oral administrations of IMI or arsenic (150 ppb) alone resulted in a significant (P < 0.05) elevation in the levels of malondialdehyde (MDA) and advanced oxidation protein product (AOPP) along with significant (P < 0.05) decline in total thiols and antioxidant enzymatic activities indicating reduced antioxidant defense in testicular tissue of exposed rats. These findings were further corroborated with histological alterations in testes like fluid accumulation in interstitial spaces in IMI administered rats. Similarly, rats provided access exclusively to arsenic-containing drinking water induced degenerative changes in seminiferous tubules in a concentration-dependent manner. Concurrent administration of IMI and arsenic produced more severe antioxidant and histopathological alterations of testes as compared to exposure to either toxicant.ConclusionsReduced antioxidant activities, increased MDA and AOPP levels with severe histopathological alterations in testes of rats on concurrent exposure indicated that IMI potentiated the arsenic-induced testicular toxicity in Wistar rats.

Abstract 1857: Hydrophilic As4S4 nanoparticles inhibit K562 cell activity through ROS modulation and autophagy induction

Abstract Realgar is crystalized As4S4 that has been demonstrated to be effective in treating hematologic malignancies by oral administration [1]. Nevertheless, the low bioavailability due to its poor solubility in neutral or acidic aqueous solution not only leads to the over dose administration of arsenic in clinical practice but also hinders the study of pharmaceutical mechanism for realgar. We previously reported a solid dispersion of realgar (e-As4S4), in which the crystal realgar (r-As4S4) was fabricated into nanoparticles encapsulated by the hydrophilic polymer using the hot melting co-extrusion technique [2]. The e-As4S4 exhibited much higher bioavailability and improved treatment efficacy in the acute myeloid leukemia (AML) animal model compared with r-As4S4. This study investigated the effect of e-As4S4 has inhibitory on K562 cells and the underlying mechanisms. We showed that e-As4S4 down regulated the cellular ROS and HIF1-alpha in a concentration dependent manner. The low concentration of e-As4S4 induced both erythroid and megakaryocytic differentiation in the cells, evidenced by the up-regulation of CD235a and CD41 respectively, and the higher concentration induced cell cycle arrested in G2/M phase and apoptosis. Consistently, the proliferation rate and oxygen-consuming rate of the cells were reduced. Meanwhile the autophagy was detected when the cells were treated with e-As4S4, as well as the variation phosphorylation for p38 and Erk. These effects together induced the significant elimination of Bcr-Abl. In conclusion, e-As4S4 induced the bi-direction differentiation by modulating cellular ROS and inducing autophagy of the cells. These results therefore suggest that e-As4S4 represents a promising orally administrated drug for the treatment of CML. Reference 1. Zhu HH et al. Oral tetra-arsenic tetra-sulfide formula versus intravenous arsenic trioxide as first-line treatment of acute promyelocytic leukemia: a multicenter randomized controlled trial. J Clin Oncol. 2013; 31:4215-21. 2. Ma Q et al. Fabrication of water-soluble polymer-encapsulated As4S4 to increase oral bioavailability and chemotherapeutic efficacy in AML mice. Sci Rep. 2016; 6: 29348. Acknowledgement This work was supported by National Key R&amp;D Program of China (2017YFA0205504) and CAMS Innovation Fund for Medical Sciences (CIFMS, 2016-I2M-3-004). Citation Format: Tao Wang, Tao Wen, Jie Meng, Jian Liu, Haiyan Xu. Hydrophilic As4S4 nanoparticles inhibit K562 cell activity through ROS modulation and autophagy induction [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1857.

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 50ppm of arsenic in drinking water for 20weeks. After 24h 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.

Ameliorative effect of diallyl trisulphide on arsenic-induced oxidative stress in rat erythrocytes and DNA damage in lymphocytes

Arsenic (As) is a naturally occurring semimetallic element that is classified as a toxicant and a human carcinogen. Diallyl trisulphide (DATS), an organosulphur compound, is an antioxidative substance that is extracted from garlic (Allium sativum). Erythrocytes are very expedient models to understand the susceptibility of membrane to oxidative damage induced by different xenobiotic compounds. Arsenic has been reported to induce oxidative stress to erythrocytes due to lipid peroxidation and alteration in defence mechanism as erythrocytes are the first target that arsenic compounds attack in the body after systemic absorption. In the light of this fact, the purpose of this study is to characterise the ameliorative effect of DATS on arsenic-induced oxidative stress in rat erythrocytes. Experimental rats were randomly divided into four groups and treated orally for 28 days: control, As [5 mg/kg body weight (BW)] treated, As+DATS (80 mg/kg BW) treated, DATS (80 mg/kg BW) treated and As+vitamin C (100 mg/kg BW) treated. Oxidative stress in erythrocytes was recorded by estimating plasma marker enzymes, plasma and erythrocyte membrane oxidative stress markers, erythrocyte membrane antioxidant enzymes and non-antioxidant enzymes, etc. Oral administration of arsenic at 5 mg/kg BW per day elevated the levels of plasma marker enzymes, namely, aspartate transaminase (AST), alanine transaminase (ALT), acid phosphatase (ACP), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and γ-glutamyl transferase (γGT) (U/L) with significantly increased lipid peroxidation markers such as thiobarbituric acid reactive substances (TBARS), malondialdehyde (MDA), lipid hydroperoxides (LH), conjugated dienes (CD), and protein carbonyl (PC) contents were also elevated in As-treated rat plasma and erythrocytes. The levels of non-enzymatic antioxidants (reduced glutathione, vitamins C and E) and enzymatic antioxidants such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST), glutathione reductase (GR), and glucose-6-phosphate dehydrogenase (G6PD) were also decreased in As-treated rats. The toxic effect of As significantly decreased the activities of membrane-bound ATPases (Na+/K+-ATPase, Mg2+-ATPase, and Ca2+-ATPase), with a significant increase in% tail DNA of rat lymphocytes measured by means of a single-cell gel electrophoresis assay. Administration of DATS for 28 days significantly reduced the levels of plasma markers. The levels of TBARS, MDA, LH, CD, and PC were significantly decreased and there was a significant increase in ATPase activities and non-enzymatic and enzymatic antioxidants on treatment with DATS in a dose-related manner. All these changes were supported by reduction of DNA damage in lymphocytes with DATS treatment. DATS at a dose of 80 mg/kg BW was found to be most effective and the results revealed the same. The results of the study showed that DATS shows a protective effect against As-induced oxidative stress in rat erythrocytes and lymphocytes.

Arsenic Exposure Affects Embryo Development of Sea Urchin, Paracentrotus lividus (Lamarck, 1816)

Toxicity tests were performed with embryos of Paracentrotus lividus to investigate the toxicological effect of two arsenic species: arsenate (As(V)), expected to be more toxic, and dimethyl-arsinate (DMA) expected to be less toxic. Exposures to toxicants were performed at different developmental stages in order to identify the most sensitive phase of embryological development. Statistical analysis revealed a high significance of each factor (Molecule, Concentration and Time of exposure) and their interaction for the dependent variable "Percentage of normal-shaped plutei". In particular, the 8 cell stage was the most sensitive to arsenic; at a concentration of 50 μg L(-1) DMA proved to be more toxic than As(V), resulting in nearly 50 % of normal-shaped plutei against the 74 % recorded for As(V). Starting the administration of arsenic at the morula stage, arsenate proved to be significantly more toxic when compared to DMA.

Arsenic in the treatment of some kinds of dermatoses

Arsenic has shown some medicinal properties in psoriasis,cutaneous T cell lymphoma,melanoma,and so on.On the one hand,arsenic at certain concentrations can suppress cell growth,induce cell apoptosis and cause the regression of skin neoplasms.On the other hand,arsenic has cytotoxicity,and can be accumulated in and induce damages to yarious organs of the human body.Epidemiological studies have shown that arsenic may be carcinogenic.Therefore,more basic research and clinical trials are warranted to optimize the therapeutic dose of arsenic so as to minimize its side effects.Individualized administration of arsenic based on gene polymorphisms associated with its side effects may enable arsenic to be an effective treatment option for some kinds of skin disorders with minimal risk. Key words: Arsenicals; Psoriasis; Lymphoma, T cell, cutaneous; Melanoma

Effects of co-administration of dietary sodium arsenate and 2,3-dimercaptopropane-1-sulfonic acid (DMPS) on the rat bladder epithelium

Inorganic arsenic is a known human carcinogen, inducing tumors of the skin, urinary bladder and lung. It is metabolized to organic methylated arsenicals. 2,3-Dimercaptopropane-1-sulfonic acid (DMPS), a chelating agent, is capable of reducing pentavalent arsenicals to the trivalent state and binding to the trivalent species, and it has been used in the treatment of heavy metal poisoning in humans. Therefore, we investigated the ability of DMPS to inhibit the cytotoxicity and regenerative urothelial cell proliferation induced by arsenate administration in vivo. Female rats were treated for 4 weeks with 100ppm AsV. DMPS (2800ppm) co-administered in the diet significantly reduced the AsV-induced cytotoxicity of superficial cells detected by scanning electron microscopy (SEM), and the incidence of simple hyperplasia observed by light microscopy and the bromodeoxyuridine (BrdU) labeling index. It also reduced the total concentration of arsenicals in the urine and the methylation of arsenic. There were no differences in oxidative stress as assessed by immunohistochemical staining for 8-hydroxy-2′-deoxyguanosine (8OHdG) of the bladder urothelium. No differences were detected in urine sediments between groups. These data suggest that DMPS has the ability to inhibit both arsenate-induced acute toxicity and regenerative proliferation of the rat bladder epithelium, most likely by decreasing exposure of the urothelium to trivalent arsenicals excreted in the urine. These data provide additional evidence that the effects of arsenate exposure in vivo do not appear to be related to oxidative effects on dG in DNA.

Intracellular, time-resolved speciation and quantification of arsenic compounds in human urothelial and hepatoma cells

In contrast to the temporary administration of arsenic in cancer therapy (e.g. in the form of arsenic trioxide), chronic exposure to low doses can cause bladder cancer and other cancers. Especially the trivalent arsenic species MMA(III) (monomethylarsonous acid) and DMA(III) (dimethylarsinous acid) are known to be highly toxic. In the present study we analysed the soluble, intracellular biotransformation products of MMA(III) in methylating HepG2 (hepatocytes) and non-methylating UROtsa cells (urothelial cells) after various times of exposure. As most of the intracellular arsenic is bound to cellular structures and proteins the soluble arsenic metabolites can hardly be speciated and even less quantified. Using an improved isolation procedure and HPLC-ICP/MS, we investigated the time-resolved biotransformation of MMA(III) and detected and quantified MMA(V) (monomethylarsonic acid) as an oxidation product of MMA(III) and, to a minor degree, DMA(V) (dimethylarsenic acid) as a methylation and oxidation product of MMA(III) in the lysates of HepG2 cells. In contrast, only MMA(V) but no DMA(V) was detected in the lysates of UROtsa cells. We conclude from our study that MMA(III) is taken up by HepG2 and UROtsa cells and immediately oxidized to MMA(V). Only in HepG2 cells MMA(V) is finally methylated to DMA(V) over time. The new method might help to advance the analysis of metabolic pathways of arsenic in mammalian cells.

Acute Arsenic Poisoning: Clinical, Toxicological, Histopathological, and Forensic Features

This report describes a suicide case by acute arsenic intoxication via intravenous injection. A 30-year-old woman injected arsenic As (V) (sodium arseniate disodique: Disodium Hydrogena Arsenik RP) in a successful suicide attempt. Three hours following administration, the woman developed severe digestive symptoms. She was admitted to a hospital and transferred to the intensive care unit within 12 h of the massive administration of arsenic. Despite therapeutic efforts, over the next 2 h she developed multiorgan failure and died. A postmortem examination was performed. Pulmonary edema and congestion of liver were apparent. As (V) and As (III) were determined by high performance liquid chromatography and inductively coupled plasma mass spectrometry after mineralization of samples by concentrated nitric acid. Toxicological analysis revealed high concentrations of arsenic in biological fluids as well as in organs. Histopathological examination showed a typical indication of myocarditis. These findings were in agreement with acute arsenic poisoning. The symptoms developed by this young woman (intoxication by intravenous administration) were comparable to oral intoxication. The clinical signs, survival time, and administration type are discussed in light of the literature on acute and chronic arsenic poisoning.