An evaluation of the nephrotoxicity of ethylenediaminetetraacetate and diethylenetriaminepentaacetate in the rat

Doolan, Paul D.; Schwartz, Sorell L.; Hayes, Jude R.; Mullen, John C.; Cummings, Nancy Boucot

doi:10.1016/0041-008x(67)90088-9

Cited by 54 publications

(13 citation statements)

References 19 publications

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“…However, this drug is compromised with serious drawbacks. For example, at high doses it might cause cell death due to necrosis (Weeden et al, 1983;Doolan et al, 1967) while, redistribution of lead from the hard tissue deposits to soft organs too has been reported (Flora et al, 1995;Cory-Slechta et al, 1987). meso-2,3-Dimercaptosuccinic acid (DMSA), an analogue of BAL, possesses a thiol group, has higher therapeutic index, water solubility (Graziano et al, 1985), and can be administered orally (Miller, 1998).…”

Section: Introductionmentioning

confidence: 99%

Beneficial role of monoesters of meso-2,3-dimercaptosuccinic acid in the mobilization of lead and recovery of tissue oxidative injury in rats

2005

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Section: Introductionmentioning

confidence: 99%

Beneficial role of monoesters of meso-2,3-dimercaptosuccinic acid in the mobilization of lead and recovery of tissue oxidative injury in rats

2005

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“…This has been the case with diethylenetriaminepentaacetic acid (DTPA),40 deferasirox,31-34 the catecholamides,41 and 1 35,42. The renal toxicity has by and large been limited to the proximal tubules.…”

Section: Introductionmentioning

confidence: 99%

Desferrithiocin Analogues and Nephrotoxicity

et al. 2008

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The syntheses of a series of 4′-O-alkylated (S)-4,5-dihydro-2-(2,4-dihydroxyphenyl)-4-methyl-4-thiazolecarboxylic acid and 5′-O-alkylated (S)-4,5-dihydro-2-(2,5-dihydroxyphenyl)-4-methyl-4-thiazolecarboxylic acid ligands are described. Their partition between octanol and water, logP app , is determined, along with their iron-clearing efficiency (ICE) in both non-iron-overloaded, bile ductcannulated rodents and in iron-overloaded primates. The ligand-promoted biliary ferrokinetics in rats are described for each of the chelators. Plots of logP app versus ICE in a rodent model for both the 4′-O-alkylated-2,4-dihydroxy and 5′-O-alkylated-2,5-dihydroxy series produced an inverse parabola plot with r 2 values of 0.97 and 0.81, respectively. The plots indicate an optimum logP app /ICE relationship. Because of the nature of the data spread in the 4′-O-alkylated 2,4-dihydroxy series, it will be used to help assess the origin of nephrotoxicity in desferrithiocin analogues: is toxicity simply related to lipophilicity, ICE, or a combination of these properties?

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“…Ces résultats, obtenus in vitro, sont en accord avec les résultats de la littérature obtenus in vivo. En effet, in vivo le DTPA n'est toxique que pour de fortes concentrations (Doolan et al, 1967) et à la dose thérapeutique de 30 µmol/kg, il n'altère ni les fonctions ni la cytologie des reins ou du foie chez le singe (Fritsch et al, 1994).…”

Section: Discussionunclassified

“…Le seul traitement proposé est le DTPA (acide diethylène-triamine-pentaacétate), utilisé pour traiter les contaminations au plutonium, alors que son efficacité pour augmenter l'excrétion du plutonium incorporé sous forme de MOX est encore mal connue (Bhattacharyya et al, 1995 ;Wood et al, 2000). De plus le DTPA est néphrotoxique lorsqu'il est administré en grande quantité (Doolan et al, 1967 ;Morgan et Smith, 1974). L'uranium étant également néphrotoxique dès qu'il atteint une concentration de 3 µg/g de rein (Diamond et al, 1989), la question est de savoir si le DTPA, administré pour réduire les risques dus au plutonium, ne risque pas de potentialiser la néphrotoxicité induite par l'uranium.…”

Section: Introductionunclassified

Synergie potentielle entre deux toxiques rénaux : le DTPA et l’uranium

et al. 2006

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RÉSUMÉABSTRACT Potential synergy between two renal toxicants: DTPA and uranium.At present, the most appropriate therapeutic approach to treat an accidental contamination with plutonium and uranium oxyde mixture (MOX) is administration of diethylene-triamine-pentaacetate acid (DTPA) in order to accelerate plutonium excretion. As uranium and DTPA are both nephrotoxic compounds, the administration of DTPA after a contamination containing uranium could enhance the nephrotoxic effects of uranium. The aim of the present work was to study in vitro on a kidney proximal tubule cell line (LLC-PK 1 ) the cytotoxicity induced by increasing concentrations of uranium in presence of 3 different chemical forms of DTPA. The results showed that the DTPA used alone induced no cytotoxicity at the concentration used here (420 µM). However, this concentration of DTPA increased the cytotoxicity induced by uranium. This increase was maximal for uranium concentrations close to the lethal concentration for 50% of the cells and reached 37, 31 and 28% for anhydrous DTPA, Na 3 CaDTPA and Na 3 ZnDTPA, respectively. These results suggest that administration of DTPA could enhance the nephrotoxicity induced by uranium.

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An evaluation of the nephrotoxicity of ethylenediaminetetraacetate and diethylenetriaminepentaacetate in the rat

Cited by 54 publications

References 19 publications

Beneficial role of monoesters of meso-2,3-dimercaptosuccinic acid in the mobilization of lead and recovery of tissue oxidative injury in rats

Beneficial role of monoesters of meso-2,3-dimercaptosuccinic acid in the mobilization of lead and recovery of tissue oxidative injury in rats

Desferrithiocin Analogues and Nephrotoxicity

Synergie potentielle entre deux toxiques rénaux : le DTPA et l’uranium

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