Nephrotoxicity of Uranium: Pathophysiological, Diagnostic and Therapeutic Perspectives

Vicente-Vicente, Laura; Quirós, Yaremi; Pérez‐Barriocanal, Fernando; López‐Novoa, José M.; López‐Hernández, Francisco J.; Morales, Ana Isabel

doi:10.1093/toxsci/kfq178

Cited by 128 publications

(65 citation statements)

References 141 publications

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“…Chronic exposure to As is associated with neuropathy, developmental disabilities, decreased IQ, numerous skin disorders, hypertension, and cancer of the skin, lungs, bladder and kidney (Abernathy et al 2003; Buchet and Lison 2000; Kapaj et al 2006; Kavcar et al 2009). Exposure to U through drinking water is another public health concern because U is a known nephrotoxicant (Kurttio et al 2006; Vicente–Vicente et al 2010). It is also a bone seeking chemical (Kurttio et al 2004) that can cause genotoxicity and developmental defects (Brugge and Buchner 2011) and bioaccumulate in bone (Kurttio et al 2004).…”

Section: Discussionmentioning

confidence: 99%

Elevated Arsenic and Uranium Concentrations in Unregulated Water Sources on the Navajo Nation, USA

Hoover

Gonzales

Shuey³

et al. 2016

Expo Health

111

102

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Regional water pollution and use of unregulated water sources can be an important mixed metals exposure pathway for rural populations located in areas with limited water infrastructure and an extensive mining history. Using censored data analysis and mapping techniques we analyzed the joint geospatial distribution of arsenic and uranium in unregulated water sources throughout the Navajo Nation, where over 500 abandoned uranium mine sites are located in the rural southwestern United States. Results indicated that arsenic and uranium concentrations exceeded national drinking water standards in 15.1% (arsenic) and 12.8% (uranium) of tested water sources. Unregulated sources in close proximity (i.e., within 6 km) to abandoned uranium mines yielded significantly higher concentrations of arsenic or uranium than more distant sources. The demonstrated regional trends for potential co-exposure to these chemicals have implications for public policy and future research. Specifically, to generate solutions that reduce human exposure to water pollution from unregulated sources in rural areas, the potential for co-exposure to arsenic and uranium requires expanded documentation and examination. Recommendations for prioritizing policy and research decisions related to the documentation of existing health exposures and risk reduction strategies are also provided.

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Section: Discussionmentioning

confidence: 99%

Elevated Arsenic and Uranium Concentrations in Unregulated Water Sources on the Navajo Nation, USA

Hoover

Gonzales

Shuey³

et al. 2016

Expo Health

111

102

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“…Ainsi une diminution de la consommation d'ATP a été observée sur des cellules rénales en cultures exposées à l'uranium. Par ailleurs, le transport du glucose ainsi que son métabolisme au sein du TCP serait également affecté après exposition à l'uranium et en ferait un 4 e transporteur altéré par l'uranium au niveau cellulaire (Goldman et al, 2006 ;Renault et al, 2010 ;Vicente-Vicente et al, 2010).…”

Section: Transporteurs D'électrolytes Et Solutésunclassified

Données nouvelles sur la néphrotoxicité de l’uranium

Guéguen

Rouas

2012

Radioprotection

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RÉSUMÉL'uranium est un radioélément ainsi qu'un métal lourd auquel l'homme peut être exposé du fait de sa présence dans l'environnement ou des activités humaines. Il exerce principalement une toxicité chimique au niveau du tubule contourné proximal du rein après exposition aiguë ou chronique. Après exposition à une forte dose d'uranium, la néphrite tubulaire aiguë est révélée par une protéinurie ainsi qu'une diminution du débit de filtration glomérulaire. Plus récemment, l'utilisation de marqueurs d'intégrité tissulaire telle que la béta 2-microglobuline ou des enzymes tissulaires a pu être corrélée aux altérations histopathologiques des tubules contournés proximaux. Lors d'exposition chronique à de faible niveau, l'utilisation de marqueurs plus spécifiques et plus sensibles s'avère nécessaire lorsque les lésions sont faibles. Des études expérimentales développées au laboratoire ont montré la pertinence de certains de ces biomarqueurs tel que Kim-1 pour détecter de faibles altérations rénales. L'uranium exerce sa cytotoxicité au niveau des cellules épithéliales des tubules contournés proximaux probablement du fait de son entrée dans la cellule où il s'accumule préférentiellement dans le noyau cellulaire, lorsqu'il n'est pas sous forme de précipités. Les mécanismes conduisant à la mort des cellules ne sont pas encore totalement élucidés mais le stress oxydant semble y jouer un rôle important. ABSTRACT New data on uranium nephrotoxicity.Uranium is an element and also a heavy metal to which humans can be exposed due to its natural presence or human activities. It has mainly a chemical toxicity on the proximal convoluted tubules of the kidney after acute or chronic exposure. At high dose exposure, acute tubular nephritis is observed, as indicated by proteinuria and a decreased glomerular filtration rate. More recently, the use of structural biomarkers such as beta 2-microglobuline or tubular enzymes has been correlated with histopathological injury of the proximal convoluted tubules. During chronic exposure at a low level, the use of some of these sensitive and specific biomarkers would be necessary, particularly when the injury is slight. Recent experimental studies in the laboratory have shown the relevance of such new biomarkers as Kim-1 to detect slight renal injury. Uranium exerts its toxicity on epithelial tubular cells in which it accumulates mainly in the nucleus when it is not precipitated. The mechanisms leading to cell death are not totally elucidated but oxidative stress seems to play an important role.

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“…The kidney is the major target organ of acute DU exposure, and DU can cause severe necrosis of renal proximal tubule endothelial cells, ultimately leading to acute renal failure or even death345. The following mechanisms of action underlie the nephrotoxicity of DU6: (1) altering ion transport in cells to inhibit the oxidative phosphorylation of mitochondria and utilization of adenosine triphosphate (ATP); (2) altering the expression of certain genes (associated with inflammation, oxidative stress, and homeostasis); and (3) increasing oxidative stress levels and decreasing anti-oxidation in cells, thus increasing DNA damage and promoting apoptosis. However, the molecular mechanisms underlying DU-induced nephrotoxicity are more complex, requiring in-depth studies to identify valuable sensitive molecular targets.…”

mentioning

confidence: 99%

Differential protein expression in metallothionein protection from depleted uranium-induced nephrotoxicity

Hao

Huang

Liu

et al. 2016

Sci Rep

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The purpose of this study was to investigate the underlying mechanism of metallothionein (MT) protection from depleted uranium (DU) using a proteomics approach to search for a DU toxicity-differential protein. MT−/− and MT+/+ mice were administrated with a single dose of DU (10 mg/kg, i.p.) or equal volume of saline. After 4 days, protein changes in kidney tissues were evaluated using a proteomics approach. A total of 13 differentially expressed proteins were identified using two-dimensional electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The validating results showed that the expression of aminoacylase-3 (ACY-3) and the mitochondrial ethylmalonic encephalopathy 1 (ETHE1) decreased significantly after DU exposure; in addition, the reduction in MT−/− mice was more significant than that in MT+/+ mice. The results also showed that exogenous ETHE1 or ACY-3 could increase the survival rate of human embryonic kidney 293 (HEK293) cells after DU exposure. A specific siRNA of ETHE1 significantly increased cell apoptosis rates after DU exposure, whereas exogenous ETHE1 significantly decreased cell apoptosis rates. In summary, ACY-3 and ETHE1 might involve in protection roles of MT. ETHE1 could be a new sensitive molecular target of DU-induced cell apoptosis.

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Nephrotoxicity of Uranium: Pathophysiological, Diagnostic and Therapeutic Perspectives

Cited by 128 publications

References 141 publications

Elevated Arsenic and Uranium Concentrations in Unregulated Water Sources on the Navajo Nation, USA

Elevated Arsenic and Uranium Concentrations in Unregulated Water Sources on the Navajo Nation, USA

Données nouvelles sur la néphrotoxicité de l’uranium

Differential protein expression in metallothionein protection from depleted uranium-induced nephrotoxicity

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