Oxidation and detoxification of trivalent arsenic species

Aposhian, H. Vasken; Zakharyan, Roksana; Avram, Mihaela D.; Kopplin, Michael J.; Wollenberg, Michael

doi:10.1016/s0041-008x(03)00324-7

Cited by 110 publications

(73 citation statements)

References 57 publications

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“…Reduction was also thought to be the means whereby DMA V was converted to DMA III in the classical pathway. The new pathway that we proposed, however, supports the suggestion of Aposhian et al 20) that oxidation is the mechanism of arsenic detoxification. 17) Recently, we demonstrated that both ATG and MADG are unstable and easily hydrolyzed to iAs III and MMA III , respectively.…”

Section: Studies On the Metabolic Pathway Of Arsenicsupporting

confidence: 87%

Elucidation of the Metabolic Pathways of Selenium and Arsenic by Analytical Toxicology

Kobayashi

2010

JOURNAL OF HEALTH SCIENCE

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Hyphenated analytical techniques, such as high-performance liquid chromatography-inductively coupled plasma-mass spectrometry (HPLC-ICP-MS) and HPLC-electrospray ionization (ESI)-MS, are powerful tools for evaluating the elemental (HPLC-ICP-MS) and molecular (ESI-MS) speciation of metalloids, such as selenium (Se) and arsenic (As). Because the toxicity of metalloids is highly dependent upon the chemical forms that are present in vivo, toxicological assessment must include both the intact compound and its metabolites. We investigated the metabolic pathways of Se and As compounds and their metabolites using HPLC-ICP-MS and HPLC-ESI-MS.

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Section: Studies On the Metabolic Pathway Of Arsenicsupporting

confidence: 87%

Elucidation of the Metabolic Pathways of Selenium and Arsenic by Analytical Toxicology

Kobayashi

2010

JOURNAL OF HEALTH SCIENCE

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“…Because DMAs V is a major urinary metabolite in human exposed to arsenic and displays less acute toxicity than either As III or As V [149,164], biomethylation has generally been considered as a major detoxification pathway for inorganic arsenicals [163]. However, intermediary metabolites of arsenic, such as MAs III and DMAs III , also possess cytocidal activity against various cell types including leukaemia and lymphoma cells [152,165,166]. Especially, MAs III was more cytocidal than As III [152].…”

Section: Metabolism and Pharmacokineticsmentioning

confidence: 99%

Application of Arsenic Trioxide Therapy for Patients with Leukaemia

Yuan

Yoshino

Kaise

et al. 2010

Biological Chemistry of Arsenic, Antimony and Bismuth

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“…1). Although the methylated species are the primary products excreted in urine, their trivalent forms (i.e., MMA III and DMA III ) are intrinsically more toxic than As III , with the pentavalent species themselves being generally nontoxic at experimental levels relevant to human environmental exposure (Aposhian et al, 2003). Notably, arsenic trioxide (As 2 O 3 ) is used clinically as a highly effective treatment of acute promyelocytic leukemia and is converted to As III and, subsequently, to methylated species in vivo after administration (Chen et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Arsenic, Reactive Oxygen, and Endothelial Dysfunction

Ellinsworth

2015

J Pharmacol Exp Ther

102

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Human exposure to drinking water contaminated with arsenic is a serious global health concern and predisposes to cardiovascular disease states, such as hypertension, atherosclerosis, and microvascular disease. The most sensitive target of arsenic toxicity in the vasculature is the endothelium, and incubation of these cells with low concentrations of arsenite, a naturally occurring and highly toxic inorganic form of arsenic, rapidly induces reactive oxygen species (ROS) formation via activation of a specific NADPH oxidase (Nox2). Arsenite also induces ROS accumulation in vascular smooth muscle cells, but this is relatively delayed because, depending on the vessel from which they originate, these cells often lack Nox2 and/or its essential regulatory cytosolic subunits. The net effect of such activity is attenuation of endothelium-dependent conduit artery dilation via superoxide anion-mediated scavenging of nitric oxide (NO) and inhibition and downregulation of endothelial NO synthase, events that are temporally matched to the accumulation of oxidants across the vessel wall. By contrast, ROS induced by the more toxic organic trivalent arsenic metabolites (monomethylarsonous and dimethylarsinous acids) may originate from sources other than Nox2. As such, the mechanisms through which vascular oxidative stress develops in vivo under continuous exposure to all three of these potent arsenicals are unknown. This review is a comprehensive analysis of the mechanisms that mediate arsenic effects associated with Nox2 activation, ROS activity, and endothelial dysfunction, and also considers future avenues of research into what is a relatively poorly understood topic with major implications for human health.

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Oxidation and detoxification of trivalent arsenic species

Cited by 110 publications

References 57 publications

Elucidation of the Metabolic Pathways of Selenium and Arsenic by Analytical Toxicology

Elucidation of the Metabolic Pathways of Selenium and Arsenic by Analytical Toxicology

Application of Arsenic Trioxide Therapy for Patients with Leukaemia

Arsenic, Reactive Oxygen, and Endothelial Dysfunction

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