In vivo assay of the potential gadolinium-induced toxicity for sensory hair cells using a zebrafish animal model

Abstract

Recently, intratympanic injection of gadolinium-based contrast agent (GdC) is growing in use to visualize the endolymphatic hydrops. Although GdC has been quite safely used over 20years through intravenous injection, the biological influence of GdC on sensory hair cells needs to be thoroughly assessed for wider clinical application of it through intratympanic injection. In this in vivo experimental study, the summated number of sensory hair cells (SO1, SO2, O1 and OC1 neuromasts) showed a steep decrease in the group exposed to 10% and 20% GdC (35.77.3, 15.09 +/- 10.82, respectively, P<.01) compared with the control group (47.18 +/- 2.30). An increase in apoptosis was also observed in the group exposed to 20% gadolinium (7.20 +/- 5.56), as compared with the control group (0.08 +/- 0.72) or the group exposed to 10% gadolinium (3.48 +/- 3.32). A significant reduction in the viable cytoplasmic mitochondria was observed in embryos exposed to 20% GdC (369 +/- 124m(2), P=.01) as compared with control embryos (447 +/- 118m(2)) or embryos exposed to 10% GdC (420 +/- 108m(2)). GdC administration did not impact peripheral neural structures. GdC caused a significant reduction in sensory hair cell counts in response to high concentrations along with increased apoptosis and mitochondrial damage. However, it may not be likely that GdC will lead to hair cell toxicity, as the estimated concentration in the inner ear after clinically tried intratympanic injection is far more diluted than the non-toxic concentration (0.625%) that was tested in this study. Increasing clinical application of intratympanic injection of gadolinium-based contrast agent (GdC) calls for a thorough assessment of its biological safety on sensory hair cell. In this in vivo experimental study, GdC caused a significant reduction in sensory hair cell counts in high concentrations (10%, 20%) along with increased apoptosis and mitochondrial damage. However, GdC will hardly lead to hair cell toxicity, as the estimated concentration in the inner ear is far more diluted than our non-toxic concentrations (0.625%).