Effect of trivalent arsenicals on cell proliferation in mouse and human microvascular endothelial cells

Dodmane, Puttappa R.; Arnold, Lora L.; Pennington, Karen L.; Singh, Rakesh K.; Cardoso, Ana Paula Ferragut; Cohen, Samuel M.

doi:10.1016/j.toxrep.2015.05.009

Cited by 6 publications

(3 citation statements)

References 33 publications

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“…The susceptibility to arsenicals varies among different tissues and organs. In fact, differential effects of As(III) and MAs(III) have been shown in hepatocytes, lung cells, microvascular endothelial cells, and urothelial cells, and, similar levels of toxicity to As(III) and MAs(III) were detected in epidermal keratinocytes. − The levels of toxicity could result from a combination of differential rates of uptake of each arsenic species and rates of arsenic methylation.…”

Section: Discussionmentioning

confidence: 94%

Comparative Cytotoxicity of Inorganic Arsenite and Methylarsenite in Human Brain Cells

Yoshinaga-Sakurai

Shinde

Rodriguez

et al. 2020

ACS Chem. Neurosci.

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The overall goal of this study is to elucidate the potential effect(s) of arsenic on a variety of human brain cells. Arsenic is the most pervasive Group A human environmental carcinogen. Long-term exposure to arsenic is associated with human diseases including cancer, cardiovascular disease, and diabetes. More immediate are the health effects on neurological development and associated disorders in infants and children exposed to arsenic in utero. Arsenic is metabolized in various organs and tissues into more toxic methylated species, including methylarsenite (MAs(III)), so the question arises whether the methylate species are responsible for the neurological effects of arsenic. Arsenic enters the brain through the blood−brain barrier and produces toxicity in the brain microvascular endothelial cells, glia (astrocytes and microglia), and neurons. In this study, we first assessed the toxicity in different types of brain cells exposed to either inorganic trivalent As(III) or MAs(III) using both morphological and cytotoxicity cell-based analysis. Second, we determined the methylation of arsenicals and the expression levels of the methylation enzyme, As(III) S-adenosylmethionine (SAM) methyltransferase (AS3MT), in several types of brain cells. We showed that the toxicity to neurons of MAs(III) was significantly higher than that of As(III). Interestingly, the differences in cytotoxicity between cell types was not due to expression of AS3MT, as this was expressed in neurons and glia but not in endothelial cells. These results support our hypothesis that MAs(III) is the likely physiological neurotoxin rather than inorganic arsenic species.

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Section: Discussionmentioning

confidence: 94%

Comparative Cytotoxicity of Inorganic Arsenite and Methylarsenite in Human Brain Cells

Yoshinaga-Sakurai

Shinde

Rodriguez

et al. 2020

ACS Chem. Neurosci.

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“…Similarly, 13 μM of either MMA III or DMA III induced cytotoxicity in human hepatocytes. , Among the inorganic and methyl arsenic species tested in human neuron cells, MMA III was most cytotoxic . In endothelial cells, MMA III and DMA III displayed significant toxicity at concentrations as low as 2.0 and 0.74 μM, respectively . Much research has also focused on the toxicity of thiolated arsenic species. , DMMTA V had particularly high toxicity, similar to that of methylated trivalent arsenic species, whereas the toxicity of DMDTA V was much lower, similar to that of MMA V and DMA V . , Based on the available data, relative toxicities of arsenic compounds are generally in the following order: MMA III , DMA III , and DMMTA V > iAs III ≫ iAs V > MMMTA V > MMA V , DMA V , and DMDTA V …”

Section: Introductionmentioning

confidence: 99%

“… 38 In endothelial cells, MMA III and DMA III displayed significant toxicity at concentrations as low as 2.0 and 0.74 μM, respectively. 40 Much research has also focused on the toxicity of thiolated arsenic species. 41 , 42 DMMTA V had particularly high toxicity, similar to that of methylated trivalent arsenic species, whereas the toxicity of DMDTA V was much lower, similar to that of MMA V and DMA V .…”

Section: Introductionmentioning

confidence: 99%

Effects of Dietary Intake of Arsenosugars and Other Organic Arsenic Species on Studies of Arsenic Methylation Efficiency in Humans

Davydiuk,

Tao,

et al. 2023

Environ. Health

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Extensive research has used dimethylarsinic acid (DMA) in urine as a marker of arsenic methylation. The premise is that humans methylate inorganic arsenicals to monomethylarsonic acid (MMA) and DMA and excrete these arsenic species into the urine. However, DMA in urine not only comes from the methylation of inorganic arsenic but also could be a result of metabolism of other arsenic species, such as arsenosugars and arsenolipids. Most environmental health and epidemiological studies of arsenic methylation might have overlooked confounding factors that contribute to DMA in urine. Here we critically evaluate reported studies that used methylation indexes, concentration ratios of methylated arsenicals, or the percentage of DMA in urine as markers of arsenic methylation efficiency. Dietary intake of arsenosugars potentially confounds the calculation and interpretation of the arsenic methylation efficiencies. Many studies have not considered incidental dietary intake of arsenosugars, arsenolipids, and other organic arsenic species. Future studies should consider the dietary intake of diverse arsenic species and their potential effect on the urinary concentrations of DMA.

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Cardiovascular adverse effects and mechanistic insights of arsenic exposure: a review

Wāng,

Ma,

Wang

et al. 2024

Environ Chem Lett

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Effect of trivalent arsenicals on cell proliferation in mouse and human microvascular endothelial cells

Cited by 6 publications

References 33 publications

Comparative Cytotoxicity of Inorganic Arsenite and Methylarsenite in Human Brain Cells

Comparative Cytotoxicity of Inorganic Arsenite and Methylarsenite in Human Brain Cells

Effects of Dietary Intake of Arsenosugars and Other Organic Arsenic Species on Studies of Arsenic Methylation Efficiency in Humans

Cardiovascular adverse effects and mechanistic insights of arsenic exposure: a review

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