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 used in pharmacology as a putative stretch-activa ted channel inhibitor. Gadodiamide, a nonionic Gd3+ chelate, is freque ntly injected i.v. into magnetic resonance imaging (MRI) to enchance c ontrast. To determine whether this complex is innocuous in humans, a c ytotoxicity study was performed on artificially stimulated human neutr ophils (HN). HN were incubated with gadodiamide and with free Gd3+ (Gd Cl3). The purpose of the study was to estimate possible cell damage af ter incubation, and to validate further trials based on stimulated cel lular models. Measurement of lactate dehydrogenase (LDH) release and t he Trypan blue exclusion test were used to assess viability. HN were s eparated from the blood of healthy volunteers and stimulated by phorbo l 12-myristate 13-acetate, an pharmacological reactive which induces p rotein kinase C activation, superoxide generation, and degranulation b y leukocytes. This study demonstrated that an acellular model is neces sary to interpret LTD results. In addition, the experimental condition s of the study demonstrated GdCl3 toxicity on HN viability, while gado diamide was not harmful.