Clinical doses of gadodiamide have no damaging effects on cochlear tissue in vitro and in vivo

Gadolinium-based contrast agents (GBCAs) are widely used in systemic magnetic resonance imaging (MRI) and can be employed in otology to evaluate endolymphatic hydrops in patients with Ménière's disease. Given the heavy metal properties of gadolinium and its tendency to deposit in tissues, it is essential to assess its ototoxic risk. We evaluated the ototoxicity of gadodiamide using in vitro and in vivo models. In vitro, cochlear explants from postnatal day 3 rats were cultured for 24 h in medium containing 0, 100 (equivalent to the concentration in perilymph after intratympanic injection), 500, or 2500 μM gadodiamide. Immunofluorescence results revealed that no significant structural damage occurred to hair cells (HCs) or spiral ganglion neuron (SGN) somata at any concentration, and that only the 2500 μM group exhibited slight thinning or disintegration of auditory nerve fibers (ANFs). In vivo, 50 μL of normal saline, 8-fold diluted, or undiluted gadodiamide was applied to the round window membrane (RWM) of adult rats via a postauricular approach. Evaluation 5 days later showed that, compared with the saline group, there were no significant changes in the compound action potential (CAP) thresholds or cochlear structures in rats treated with either 8-fold diluted or undiluted gadodiamide. The results confirmed that clinical doses of gadodiamide do not cause damage to cochlear structures; however, the neurotoxicity observed at excessively high concentrations highlights the necessity of strict adherence to dosing protocols.