Effect of chronic intake of arsenic-contaminated water on liver

Mazumder, D. N. Guha

doi:10.1016/j.taap.2004.08.025

Cited by 255 publications

(173 citation statements)

References 24 publications

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“…The data in the current study differ significantly from previous rodent studies of arsenic effects on the liver vasculature (Bashir et al, 2006;Das et al, 2005;Flora et al, 1997;Mazumder, 2005). The major contrast is that in the current study, vascular remodeling was observed following sub-chronic exposure to a moderate arsenic exposure.…”

Section: Discussioncontrasting

confidence: 99%

“…Liver injury in response to arsenic has been proposed to be mediated by oxidative stress and increased levels of inflammatory cytokines (Das et al, 2005;Mazumder, 2005). Das et al showed that nine months was required before overt liver injury was observed in response to high levels of arsenic and that this injury was associated with increased oxidative damage and cytokine release (Das et al, 2005).…”

Section: Discussionmentioning

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). However, the number of studies that examine thresholds and mechanisms for the vascular effects of environmentally or human relevant arsenic exposures is limited.…”

Section: Introductionmentioning

confidence: 99%

“…The liver is the major organ for arsenic metabolism and the blood in the liver vessels should have one of the highest levels of inorganic arsenic and its metabolites found in the body following exposure to arsenic in drinking water. Liver effects associated with arsenic in drinking water include non-cirrhotic liver fibrosis and to a lesser extent portal hypertension (Mazumder, 2005;Das et al, 2005;Guha Mazumder, 2003). These pathologies are distinguished by increased vascular channels in the portal regions of the liver.…”

Section: Introductionmentioning

confidence: 99%

“…In addition, cardiac and liver disorders are the major side effects of therapeutic arsenic regimes used to treat leukemia (Shigeno et al, 2005). Despite epidemiological evidence that the liver vasculature is a pathogenic target of chronic arsenic ingestion (Mazumder, 2005), the direct effects of arsenic on the liver vascular cells remain unknown.…”

Section: Introductionmentioning

confidence: 99%

See 4 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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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: Discussioncontrasting

confidence: 99%