Arsenic induces oxidant stress and NF-KB activation in cultured aortic endothelial cells

Barchowsky, Aaron; Dudek, Edward J.; Treadwell, Melinda D.; Wetterhahn, Karen E.

doi:10.1016/0891-5849(96)00174-8

Cited by 270 publications

(162 citation statements)

References 31 publications

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“…In vivo, high doses of arsenic affect all cells in the liver and promote a significant amount of apoptosis in hepatocytes (Bashir et al, 2006). High doses of arsenic (>5 μM) are known to be toxic to endothelial cells (Barchowsky et al, 1996;Barchowsky et al, 1999;Kao et al, 2003;Roboz et al, 2000) and it is possible that high dose exposures elicit multiple mechanisms for toxicity that mask the pathogenic mechanisms mediating liver diseases in response to environmentally relevant arsenic exposures. In contrast, the current study investigated effects of a relevant ad libitum ingestion of drinking water containing an arsenic level that was near the threshold for observing significant liver disease in humans (250 ppb = ∼ 0.7-.9 μg/mouse/ day for 5 weeks; human equivalent ∼ 32 μg/day for 3.75 years).…”

Section: Discussionmentioning

confidence: 99%

“…Pathogenic endothelial cell activation and angiogenesis in rodent models are sensitive to low, environmentally relevant arsenic exposures (Soucy et al, 2003;Soucy et al, 2005;Kamat et al, 2005). Arsenic stimulates the angiogenic process in cultured cells and neovascularization in vivo (Barchowsky et al, 1996;Kao et al, 2003;Kamat et al, 2005;Liu et al, 2006;Soucy et al, 2003;Soucy et al, 2005). However, this stimulation occurs only at low to moderate concentrations of arsenic (5-500 ppb in vivo, 0.1-5.0 μM in cell culture; (Barchowsky et al, 1996;Kao et al, 2003;Soucy et al, 2003;Soucy et al, 2005)).…”

Section: Introductionmentioning

confidence: 99%

“…Arsenic stimulates the angiogenic process in cultured cells and neovascularization in vivo (Barchowsky et al, 1996;Kao et al, 2003;Kamat et al, 2005;Liu et al, 2006;Soucy et al, 2003;Soucy et al, 2005). However, this stimulation occurs only at low to moderate concentrations of arsenic (5-500 ppb in vivo, 0.1-5.0 μM in cell culture; (Barchowsky et al, 1996;Kao et al, 2003;Soucy et al, 2003;Soucy et al, 2005)). Concentrations of arsenic above 5 μM are toxic to confluent endothelial cells and limit tube formation in culture (Barchowsky et al, 1996;Roboz et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

“…However, this stimulation occurs only at low to moderate concentrations of arsenic (5-500 ppb in vivo, 0.1-5.0 μM in cell culture; (Barchowsky et al, 1996;Kao et al, 2003;Soucy et al, 2003;Soucy et al, 2005)). Concentrations of arsenic above 5 μM are toxic to confluent endothelial cells and limit tube formation in culture (Barchowsky et al, 1996;Roboz et al, 2000). Arsenic is more toxic to sub-confluent endothelial cells (Barchowsky et al, 1996) and the threshold for in vivo approximately 1-5 stimulate vascular smooth muscle cells to proliferate and to increase vascular endothelial cell toxicity in angiogenesis assays is μM (Soucy et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

“…Concentrations of arsenic above 5 μM are toxic to confluent endothelial cells and limit tube formation in culture (Barchowsky et al, 1996;Roboz et al, 2000). Arsenic is more toxic to sub-confluent endothelial cells (Barchowsky et al, 1996) and the threshold for in vivo approximately 1-5 stimulate vascular smooth muscle cells to proliferate and to increase vascular endothelial cell toxicity in angiogenesis assays is μM (Soucy et al, 2003). In contrast, high levels of arsenic (10-50 μM) growth factor (VEGF) expression and secretion (Soucy et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

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Low level arsenic promotes progressive inflammatory angiogenesis and liver blood vessel remodeling in mice

Straub

Stolz

Vin

et al. 2007

Toxicology and Applied Pharmacology

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The vascular effects of arsenic in drinking water are global health concerns contributing to human disease worldwide. Arsenic targets the endothelial cells lining blood vessels and endothelial cell activation or dysfunction may underlie the pathogenesis of both arsenic-induced vascular diseases and arsenic-enhanced tumorigenesis. The purpose of the current studies was to demonstrate that exposing mice to drinking water containing environmentally relevant levels of arsenic promoted endothelial cell dysfunction and pathologic vascular remodeling. Increased angiogenesis, neovascularization, and inflammatory cell infiltration was observed in Matrigel plugs implanted in C57BL/6 mice following 5 week exposures to 5-500 ppb arsenic (Soucy et al., 2005). Therefore, functional in vivo effects of arsenic on endothelial cell function and vessel remodeling in an endogenous vascular bed were investigated in the liver. Liver sinusoidal endothelial cells (LSEC) became progressively defenestrated and underwent capillarization to decrease vessel porosity following exposure to 250 ppb arsenic for 2 weeks. Sinusoidal expression of PECAM-1 and laminin-1 proteins, a hallmark of capillarization, was also increased by 2 weeks of exposure. LSEC caveolin-1 protein and caveolae expression were induced after 2 weeks of exposure indicating a compensatory change. Likewise, CD45/CD68 positive inflammatory cells did not accumulate in the livers until after LSEC porosity was decreased; indicating that inflammation is a consequence and not a cause of the arsenic-induced LSEC phenotype. The data demonstrate that the liver vasculature is an early target of pathogenic arsenic effects and that the mouse liver vasculature is a sensitive model for investigating vascular health effects of arsenic.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Low level arsenic promotes progressive inflammatory angiogenesis and liver blood vessel remodeling in mice

Straub

Stolz

Vin

et al. 2007

Toxicology and Applied Pharmacology

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Differential effects of arsenic(III) and chromium(VI) on nuclear transcription factor binding

et al. 1999

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The toxic metals arsenic(III) and chromium(VI) are considered human carcinogens, although they may act through different mechanisms. We previously showed that when administered at single low, non-overtly toxic doses, chromium, arsenic, and several other chemical carcinogens preferentially alter expression of several model inducible genes in both whole-animal and cell-culture systems. In this study, we assessed whether chromium and arsenic target specific signaling pathways within cells to selectively modulate gene expression. We examined the effects of non-cytotoxic and cytotoxic doses of arsenic(III) and chromium(VI) on nuclear binding of the transcription factors AP-1, NF-kappaB, Sp1, and YB-1 in human MDA-MB-435 breast cancer and rat H4IIE hepatoma cells. These transcription factors were chosen because they may regulate many inducible genes, including those previously shown to be altered by metal treatments. We report that both arsenic and chromium significantly altered nuclear binding levels of these factors to their respective cis-acting elements. However, there were qualitative and quantitative differences in these effects that were dependent on the metal, time, dose, transcription factor, and cell line. These effects may play a significant role in metal-induced alterations in gene expression.

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Arsenic, Antimony, and Bismuth

Madden

Fowler²

2023

Patty's Toxicology

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Arsenic, Antimony, and Bismuth are members of Group V of the Periodic Table of Elements. These elements have been used for a variety of medicinal and pest control purposes over a number of centuries. They have also been used in metallic alloys and in the production of III–V semiconductors to increase electronic speeds of computer chips. Arsenicals are largely metabolized by methylation pathways and bismuth is known to induce the metal‐binding protein metallothionein and to form electron–dense cytoplasmic and intranuclear inclusion bodies.

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Arsenic induces oxidant stress and NF-KB activation in cultured aortic endothelial cells

Cited by 270 publications

References 31 publications

Low level arsenic promotes progressive inflammatory angiogenesis and liver blood vessel remodeling in mice

Low level arsenic promotes progressive inflammatory angiogenesis and liver blood vessel remodeling in mice

Differential effects of arsenic(III) and chromium(VI) on nuclear transcription factor binding

Arsenic, Antimony, and Bismuth

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