Gadoteric Acid and Gadolinium: Exploring Short- and Long-Term Effects on Healthy Animals.

Regarding the safety of gadolinium (Gd (III))-based contrast agents, we aimed to evaluate the short- and long-term effects following a single exposure to gadoteric acid (DOTA) or to free Gd (III) using animal models. Biomarkers of kidney injury, inflammation, iron metabolism, dyslipidemia, hepatic and hematologic disturbances and kidney histopathological and differential gene expression (DGE) analyses were evaluated. In the short-term study, compared to the controls, exposure to Gd (III) was associated with higher inflammation; changes in lipid, iron and hepatic metabolisms; hematological alterations; and kidney damage. Exposure to DOTA revealed changes in hematological, lipid and hepatic biomarkers. In the long-term study, compared to the controls, exposure to Gd (III) or to DOTA showed much fewer changes than the short-term exposure. Comparing the kidney gene expression of Gd (III) or DOTA exposure versus the control, we found clearly different DGE patterns and a lower number of differently expressed genes in the long-term study, for both compounds. Our data show that a single-dose exposure to these compounds induces several short-term changes which over time return to normal or are sustained, although with less severity, especially in the case of DOTA.