An investigation of the effects of the gadolinium and gadolinium chelates on the intracellular calcium in the different cell cultures

Gadolinium (Gd3+) is a rare earth metal that occurs in only trace amounts biologically and is not known to have a metabolic role but shown to inhibit calcium channels. Gd based MR contrast agents (GBMCA) are manufactured by a chelating process, in which organic ligand molecules form a stable complex around Gd3+. Aim of this study is to investigate the probably effect of free gadolinium and GBMCA in neuron cell lines on the intracellular Ca2+ because these agents can dissociate and result in release of toxic Gd3+ ions in metabolic conditions.Dorsal root ganglia (DRG), trigeminal ganglia (TG) and GT1 7 (immortalized GnRH neurons) cells were studied for responses to agents and nonspecific depolarization by high KCl+ and melatonin, respectively, by monitoring changes in [Ca2+]i with a microscopic digital image analysis system in Fura 2 AM loaded neurons.GBMCA and molecular gadolinium were prepared at 0.1 mmol/kg doses at the same pH and temperature values and administrated to the cell lines that loaded to calcium sensitive fluorescent dye Fura 2 AM.Application of Gd3+ and gadodiamid on the rat DRG and TG neurons caused significant decreases in the basal intracellular calcium levels whereas gadoterat meglumine did not have a significant impact. Gd3+ was more effective than gadodiamide. While returned effect was almost complete with gadodiamid, Gd3+ has irreversible effect. GT1 7 cell lines showed the same responses as Gd3+ and meglumine gadoterat in DRG and TG. The degree of effect of meglumine gadoterat is neglectable compared to Gd3+ and gadodiamid although it showed gadodiamid-like effects.In conclusion, some of the gadolinium chelates may release gadolinium in physiological conditions and cause toxic effects by changing the levels of intracellular calcium levels.