Vascular Effects of Chronic Arsenic Exposure: A Review

Engel, Robert; Hopenhayn‐Rich, Claudia; Receveur, Olivier; Smith, Allan H.

doi:10.1093/oxfordjournals.epirev.a036150

Cited by 207 publications

(106 citation statements)

References 89 publications

(161 reference statements)

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“…Previous research of the effects of chronic exposure to iAs has focused primarily on its carcinogenic potential. However, chronic exposures to iAs from the environment or in occupational settings have also been linked to non-carcinogenic diseases, including peripheral vascular disease, cardiovascular and cerebrovascular diseases Chen et al, 1996;Chiou et al, 1997;Engel et al, 1994;Thomas and Goyer, 1995;Tseng et al, 1995;Tseng et al, 1997), hypertension , goiter (Chang et al, 1991), hepatomegaly (Santra et al, 1999), respiratory system dysfunction (Mazumder et al, 2000), nervous system dysfunction (Bencko et al, 1977;Chisolm Jr. and Thomas, 1983;Masahiko and Hideyasu, 1973), and diabetes mellitus (Lai et al, 1994;Rahman et al, 1998;Rahman et al, 1999;Tseng et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Examination of the effects of arsenic on glucose homeostasis in cell culture and animal studies: Development of a mouse model for arsenic-induced diabetes

Paul

Hernández-Zavala

Walton

et al. 2007

Toxicology and Applied Pharmacology

125

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Previous epidemiologic studies found increased prevalences of type 2 diabetes mellitus in populations exposed to high levels of inorganic arsenic (iAs) in drinking water. Although results of epidemiologic studies in low-exposure areas or occupational settings have been inconclusive, laboratory research has shown that exposures to iAs can produce effects that are consistent with type 2 diabetes. The current paper reviews the results of laboratory studies that examined the effects of iAs on glucose metabolism and describes new experiments in which the diabetogenic effects of iAs exposure were reproduced in a mouse model. Here, weanling male C57BL/6 mice drank deionized water with or without the addition of arsenite (25 or 50 ppm As) for 8 weeks. Intraperitoneal glucose tolerance tests revealed impaired glucose tolerance in mice exposed to 50 ppm As, but not to 25 ppm As. Exposure to 25 and 50 ppm As in drinking-water resulted in proportional increases in the concentration of iAs and its metabolites in the liver and in organs targeted by type 2 diabetes, including pancreas, skeletal muscle and adipose tissue. Dimethylarsenic was the predominant form of As in the tissues of mice in both 25 and 50 ppm groups. Notably, the average concentration of total speciated arsenic in livers from mice in the 50 ppm group was comparable to the highest concentration of total arsenic reported in the livers of Bangladeshi residents who had consumed water with an order of magnitude lower level of iAs. These data suggest that mice are less susceptible than humans to the diabetogenic effects of chronic exposure to iAs due to a more efficient clearance of iAs or its metabolites from target tissues.

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Section: Introductionmentioning

confidence: 99%

Examination of the effects of arsenic on glucose homeostasis in cell culture and animal studies: Development of a mouse model for arsenic-induced diabetes

Paul

Hernández-Zavala

Walton

et al. 2007

Toxicology and Applied Pharmacology

125

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“…The vascular effects of arsenic in drinking water pose a global public health concern and contribute to disease in tens of millions of people worldwide (reviewed in (Navas-Acien et al, 2005;Engel et al, 1994). While the roles of environmental contaminants in the etiology of vascular diseases and in the vascular contributions to organ dysfunction remain poorly defined, epidemiological studies have associated arsenic exposures with increased risk of cardiovascular diseases (Navas-Acien et al, 2005;Wu et al, 2006;Tseng et al, 2003;Engel et al, 1994) and vascular contributions to liver disease (Mazumder, 2005).…”

Section: Introductionmentioning

confidence: 99%

“…While the roles of environmental contaminants in the etiology of vascular diseases and in the vascular contributions to organ dysfunction remain poorly defined, epidemiological studies have associated arsenic exposures with increased risk of cardiovascular diseases (Navas-Acien et al, 2005;Wu et al, 2006;Tseng et al, 2003;Engel et al, 1994) and vascular contributions to liver disease (Mazumder, 2005). Recent reports indicated that high environmental levels of arsenic (10-100 ppm in drinking water) accelerate atherosclerosis (Bunderson et al, 2004;Simeonova et al, 2003) and promote liver vascular channel formation in rodent models (Mazumder, 2005).…”

Section: Introductionmentioning

confidence: 99%

“…In contrast, high levels of arsenic (10-50 μM) growth factor (VEGF) expression and secretion (Soucy et al, 2004). The proliferation of the smooth muscle cells may contribute to the atherogenic effects and vessel dysfunction seen following arsenic exposures in humans (Engel et al, 1994;Penn, 1990). VEGF is a primary factor for stimulating angiogenesis and plays a critical role in pathological angiogenesis in both atherosclerosis and tumors (Aggarwal et al, 2006;Carmeliet, 2000;Dalgleish et al, 2006;Hayden 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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“…Arsenic, a natural constituent of soil and water, is a well-known human carcinogen [1,2]. Chronic exposure to inorganic forms of it from drinking water and air pollution can cause many types of cancers such as skin cancer, bladder cancer, liver cancer and kidney cancer.…”

Section: Introductionmentioning

confidence: 99%

The role of Akt on Arsenic trioxide suppression of 3T3-L1 preadipocyte differentiation

et al. 2005

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The present study investigates the molecular details of how arsenic trioxide inhibits preadipocyte differentiation and examines the role of Akt/PKB in regulation of differentiation and apoptosis. Continual exposure of arsenic trioxide, at the clinic achievable dosage that does not induce apoptosis, suppressed 3T3-L1 cell differentiation into fat cells by inhibiting the expression of PPARγ and C/EBPα and disrupting the interaction between PPARγ and RXRα, which determines the programming of the adipogenic genes. Interestingly, if we treated the cells for 12 or 24 h and then withdrew arsenic trioxide, the cells were able to differentiate to the comparable levels of untreated cells as assayed by the activity of GAPDH, the biochemical marker of preadipocyte differentiation. Long term treatment blocked the differentiation and the activity of GAPDH could not recover to the comparable levels of untreated cells. Continual exposure of arsenic trioxide caused accumulation in G2/M phase and the accumulation of p21. We found that arsenic trioxide induced the expression and the phosphorylation of Akt/PKB and it inhibited the interaction between Akt/PKB and PPARγ . Akt/PKB inhibitor appears to block the arsenic trioxide suppression of differentiation. Our results suggested that Akt/PKB may play a role in suppression of apoptosis and negatively regulate preadipocyte differentiation.

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Vascular Effects of Chronic Arsenic Exposure: A Review

Cited by 207 publications

References 89 publications

Examination of the effects of arsenic on glucose homeostasis in cell culture and animal studies: Development of a mouse model for arsenic-induced diabetes

Examination of the effects of arsenic on glucose homeostasis in cell culture and animal studies: Development of a mouse model for arsenic-induced diabetes

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

The role of Akt on Arsenic trioxide suppression of 3T3-L1 preadipocyte differentiation

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