Free gadolinium and gadodiamide, a gadolinium chelate used in magnetic resonance imaging: evaluation of their in vitro effects on human neutrophil viability.
Gadolinium (Gd3+) is known to be the most paramagnetic ion but is also a very toxic cation often used in pharmacology as a putative stretch-activated channel inhibitor. Gadodiamide, a nonionic Gd3+ chelate, is frequently injected i.v. into magnetic resonance imaging (MRI) to enhance contrast. To determine whether this complex is innocuous in humans, a cytotoxicity study was performed on artificially stimulated human neutrophils (HN). HN were incubated with gadodiamide and with free Gd3+ (GdCl3). The purpose of the study was to estimate possible cell damage after incubation, and to validate further trials based on stimulated cellular models. Measurement of lactate dehydrogenase (LDH) release and the Trypan blue exclusion test were used to assess viability. HN were separated from the blood of healthy volunteers and stimulated by phorbol 12-myristate 13-acetate, a pharmacological reactive which induces protein kinase C activation, superoxide generation, and degranulation by leukotcytes. This study demonstrated that an acellular model is necessary to interpret LDH results. In addition, the experimental conditions of the study demonstrated GdCl3 toxicity on HN viability, while gadodiamide was not harmful.
Behra-Miellet
J
J
University of Lille, Faculty of Pharmaceutical and Biological Sciences, Laboratory of Pharmacology, Pharmacokinetics and Clinical Pharmacy, France.
Gressier
B
B
Brunet
C
C
Dine
T
T
Luyckx
M
M
Cazin
M
M
Cazin
J C
JC
D000704:Analysis of Variance; D003287:Contrast Media / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005682:Gadolinium / Q000494:pharmacology*; D019786:Gadolinium DTPA; D006801:Humans; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000379:methods; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D009942:Organometallic Compounds / Q000494:pharmacology*; D004369:Pentetic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D014343:Trypan Blue
D003287:Contrast Media; D009942:Organometallic Compounds; D004369:Pentetic Acid; C064925:gadodiamide; D005682:Gadolinium; D007770:L-Lactate Dehydrogenase; D014343:Trypan Blue; D019786:Gadolinium DTPA