Effects of gadolinium contrast agents in naïve and nephrectomized rats: Relevance to nephrogenic systemic fibrosis

Grant, Derek; Johnsen, Harald; Juelsrud, A.; Løvhaug, Dagfinn

doi:10.1080/02841850802637808

Cited by 43 publications

(37 citation statements)

References 19 publications

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“…The rats showed increased dermal cellularity composed of dendritic-like cells and spindle-shaped fibrocytes (probably fibroblasts) (11,13) similar to those observed in human NSF patients (5). In a different rat study, skin lesions seen after Omniscan and gadodiamide (Omniscan without excess ligand) treatment were attributed to excessive scratching rather than an NSF-like disease process (23). This hypothesis seems unlikely since, in several studies, the increased cellularity but also the infiltration of CD34-positive was also observed after GBCAs injection in animals without ulcerations (11)(12)(13)24).…”

Section: Nsf Animal Modelsmentioning

confidence: 77%

Gadolinium‐based contrast agents and NSF: Evidence from animal experience

Sieber

Steger‐Hartmann

Lengsfeld

et al. 2009

Magnetic Resonance Imaging

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Nephrogenic systemic fibrosis (NSF) is a potentially severe systemic disease typically characterized by fibrosis of the skin and connective tissues. The etiology of NSF is still unknown but is likely to be multifactorial. Specific triggers under scientific evaluation have included surgery and/or the occurrence of thrombosis or other vascular injury, proinflammatory state, the administration of high doses of erythropoietin, and more recently the use of gadolinium-based contrast agents (GBCAs). The aim of this review is to summarize knowledge regarding the pathogenesis of NSF and the potential role of GBCAs in its pathology, with a focus on animal experiments. The potential role of complex stability of GCBAs will be highlighted by results from several in vitro and in vivo experiments in rodent models of NSF.

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Section: Nsf Animal Modelsmentioning

confidence: 77%

Gadolinium‐based contrast agents and NSF: Evidence from animal experience

Sieber

Steger‐Hartmann

Lengsfeld

et al. 2009

Magnetic Resonance Imaging

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“…Most non-clinical and clinical studies available to date favour a causal role of dissociated Gd in tissues in the pathogenesis of NSF (Abraham et al, 2008;Fretellier et al, 2011bFretellier et al, , 2012Fretellier et al, , 2013Haylor et al, 2012;Idée et al, 2014;Pietsch et al, 2009;Sieber et al, 2008a,b,c;Wadas et al, 2010), although this hypothesis remains disputed by some authors (Grant et al, 2009;Wermuth and Jimenez, 2014). Basically, GCs differ in their ability to release dissociated Gd, with macrocyclic GCs being kinetically more stable than linear agents and linear ionic compounds being thermodynamically more stable than linear non-ionic GCs (Port et al, 2008).…”

Section: Introductionmentioning

confidence: 93%

Distribution profile of gadolinium in gadolinium chelate-treated renally-impaired rats: Role of pharmaceutical formulation

Fretellier

Salhi

Schroeder

et al. 2015

European Journal of Pharmaceutical Sciences

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“…Interestingly, the NSF-like skin lesions were observed in the animals with the highest gadolinium concentration in the skin (66). The relevance of these models was challenged in a study carried out in naïve and 5/6 nephrectomized rats receiving very high doses of GC (up to 10 mmol/kg of Gd-DTPA-BMA) (67). The authors suggested that skin lesions found in Gd-DTPA-BMA-treated animals were caused by Gd-DTPA-BMA-specific intensive pruritus and scratching.…”

Section: Inertia Of Gadolinium Chelates: Biological Studiesmentioning

confidence: 99%

Role of thermodynamic and kinetic parameters in gadolinium chelate stability

Idée

Port

Robic

et al. 2009

Magnetic Resonance Imaging

164

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In recent years there has been a renewed interest in the physicochemical properties of gadolinium chelates (GC). The aim of this review is to discuss the physicochemical properties of marketed GC with regard to possible biological consequences. GC can be classified according to three key molecular features: 1) the nature of the chelating moiety: either macrocyclic molecules in which Gd 3þ is caged in the preorganized cavity of the ligand, or linear, openchain molecules; 2) ionicity: the ionicity of the molecule varies from neutral to tri-anionic agents; and 3) the presence or absence of an aromatic lipophilic moiety, which has a profound impact on the biodistribution of the GC. These parameters can also explain why GC differ considerably with regard to their thermodynamic stability constants and kinetic stability, as demonstrated by numerous studies. The concept of thermodynamic and kinetic stability is critically discussed, as it remains somewhat controversial, especially in predicting the amount of free gadolinium that may result from decomplexation of chelates in physiologic or pathologic situations. This review examines the possibility that the high kinetic stability provided by the macrocyclic structure combined with a high thermodynamic stability (reinforced by ionicity for macrocyclic chelates) can minimize the amount of free Gd 3þ released in the body.

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Effects of gadolinium contrast agents in naïve and nephrectomized rats: Relevance to nephrogenic systemic fibrosis

Abstract: The visible skin lesions seen in this study appeared to be caused by excessive scratching in response to pruritus. As there was no evidence of dermal fibrosis, the cardinal feature of human NSF, this did not appear to be a model of human NSF.

Cited by 43 publications

References 19 publications

Gadolinium‐based contrast agents and NSF: Evidence from animal experience

Gadolinium‐based contrast agents and NSF: Evidence from animal experience

Distribution profile of gadolinium in gadolinium chelate-treated renally-impaired rats: Role of pharmaceutical formulation

Role of thermodynamic and kinetic parameters in gadolinium chelate stability

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