Disease relevance of arsenic

• Letter: Arsenic and non-cirrhotic portal hypertension [1].
• Toxic hepatitis, cirrhosis, noncirrhotic portal hypertension, and hemangiosarcoma of the liver have been reported with the intake of arsenicals [2].
• INTERVENTION: Arsenic trioxide, 0.15 mg/kg of body weight, administered daily by 2-hour infusion for a maximum of 60 days [3].
• Arsenic compounds have recently been shown to induce high rates of complete remission in patients with acute promyelocytic leukemia (APL) [4].
• Buthionine Sulfoximine Enhancement of Arsenic Trioxide-Induced Apoptosis in Leukemia and Lymphoma Cells Is Mediated via Activation of c-Jun NH2-Terminal Kinase and Up-regulation of Death Receptors [5].

Psychiatry related information on arsenic

• Animals exposed to different concentrations of test chemicals (Copper, Arsenic and HCH) showed prominent behavioural/morphological alterations viz., coughing, redness on the ventral side, paralysis and disorientation in scaphognathite activity [6].

High impact information on arsenic

• Toxicology. Arsenic researchers face isotope shortage [7].
• BACKGROUND: Arsenic trioxide (As2O3) can induce clinical remission in patients with acute promyelocytic leukemia via induction of differentiation and programmed cell death (apoptosis) [8].
• Leishmania resistant to arsenicals and antimonials extrude arsenite [9].
• Trypanothione overproduction and resistance to antimonials and arsenicals in Leishmania [9].
• Arsenic compounds have been abundant at near toxic levels in the environment since the origin of life [10].

Chemical compound and disease context of arsenic

• The ArsA protein, the catalytic subunit of the oxyanion-translocating ATPase responsible for resistance to arsenicals and antimonials in Escherichia coli, is activated by arsenite or antimonite [11].
• The plasmid-borne arsenical resistance (ars) operon encodes an arsenical-translocating ATPase and confers resistance to antimonials and arsenicals in Escherichia coli by extrusion of the toxic compounds from the cytosol [12].
• Dimethylarsinic acid (DMA) is a major metabolite of inorganic arsenicals, which are epidemiologically significant chemicals in relation to liver cancer in mammals [13].
• To evaluate the possibility that DMA(V) administration produces urothelial toxicity and regeneration by the formation of trivalent arsenicals, 2,3-dimercaptopropane-1-sulfonic acid (DMPS, 5600 ppm), a chelator of trivalent arsenicals, was co-administered with DMA(V) (100 ppm) for 2 weeks to groups of female Fischer F344 rats [14].
• Direct cardiac effects of As2O3 in rabbits: evidence of reversible chronic toxicity and tissue accumulation of arsenicals after parenteral administration [15].

Biological context of arsenic

• The ars operon of the conjugative R-factor R773 encodes an oxyanion pump that catalyzes extrusion of arsenicals from cells of Escherichia coli [16].
• An oxyanion-translocating ATPase encoded by a bacterial plasmid confers resistance to antiomonials and arsenicals in Escherichia coli by extrusion of the toxic oxyanions from the cytosol [17].
• ArsA is the catalytic subunit of the arsenical pump, coupling ATP hydrolysis to the efflux of arsenicals through the ArsB membrane protein [18].
• RESULTS: Arsenic trioxide induced mitotic arrest starting at 24 hours and significant cell death at 48 hours [19].
• The finding of MMAIII and DMAIII in human urine, along with recent studies showing the high toxicity of these arsenicals, suggests that the usual belief of arsenic detoxification by methylation needs to be reconsidered [20].

Anatomical context of arsenic

• The second tool is trivalent arsenical affinity chromatography, which we use to show novel direct interactions between trivalent arsenicals and several proteins from 3T3-L1 adipocytes including the insulin-responsive glucose transporter GLUT4, the insulin proreceptor, and both the alpha and beta subunits of tubulin [21].
• In the SCG assay in human lymphocytes, methylated trivalent arsenicals were much more potent than any other arsenicals that were tested [22].
• BACKGROUND: Arsenic trioxide induces growth inhibition and apoptosis in human hepatocellular carcinoma (HCC) cell lines [23].
• Retention of arsenic within the erythrocytes of rats fed the highest level of fish arsenic were equal to controls whereas it was about 130 times higher than controls among rats fed the highest level of arsenic as cacodylic acid [24].
• Arsenicals inhibit thioredoxin reductase in cultured rat hepatocytes [25].

Associations of arsenic with other chemical compounds

• Dimethylarsinic acid (cacodylic acid; DMA) is one of the major methylated metabolites of ingested arsenicals in most mammals [26].
• Cationic discontinuous electrophoresis can be carried out at pH 6.0 With excellent resolution in urea-containing acrylamide gels with potassium as the leading ion, 3-picoline as the trailing ion, and cacodylic acid as the buffer [27].
• Uptake of pentamidine in Trypanosoma brucei brucei is mediated by three distinct transporters: implications for cross-resistance with arsenicals [28].
• Phenylarsine oxide (PhAsO) and other tervalent organic arsenicals inhibited in a dose-dependent manner hepatic glycogenolysis, vasoconstriction, Ca2+ mobilization and the stimulated O2 consumption caused by immune-aggregate infusion [29].
• Inhibition results from reaction at a dithiol that can be protected by nonpermeant mercurials, oxidants, and arsenicals as well as by phosphorylation of EII [30].

Gene context of arsenic

• ATR, PML, and CHK2 Play a Role in Arsenic Trioxide-induced Apoptosis [31].
• RESULTS: Both arsenicals activated ERK1/2, which are most highly activated in response to mitogenic stimulation, in addition to JNK and p38, which show greater activation in response to cellular stresses [32].
• Both arsenicals transiently activated ERK1/2 prior to JNK and p38 activation [32].
• Both arsenicals stimulated tyrosine phosphorylation of EGFR and Shc [32].
• Metallothionein-I/II null mice are more sensitive than wild-type mice to the hepatotoxic and nephrotoxic effects of chronic oral or injected inorganic arsenicals [33].

Analytical, diagnostic and therapeutic context of arsenic

• Although numerous epidemiological studies have shown that inorganic arsenicals cause skin cancers and hyperkeratoses in humans, there are currently no established mechanisms for their action or animal models [34].
• Poly[d(A-T).d(A-T)] and poly[d(G-C).d(G-C)], each dissolved in 0.1 M NaClO4, 5 mM cacodylic acid buffer, pH 6.8, experience inversion of their circular dichroism (CD) spectrum subsequent to the addition of Hg(ClO4)2 [35].
• OBJECTIVE: We assessed the associations of general hypertension with nutrient intakes and diet patterns in Bangladesh. DESIGN: This was a cross-sectional analysis of 11 116 participants enrolled in the Health Effects of Arsenic Longitudinal Study in Bangladesh. Dietary intakes were measured by use of a validated food-frequency questionnaire [36].
• It was installed into a system of liquid chromatography (LC) combined with inductively coupled plasma mass spectrometry (ICPMS) using a hydride generation (HG) technique to enable sensitive speciation of organic arsenicals [37].
• In reaction mixtures containing recombinant rat AS3MT (rrAS3MT) and radiolabeled arsenite, mono- and dimethylated arsenicals and a third radiolabeled product can be resolved by thin-layer chromatography [38].

References