Cytogenotoxic Activity of Gadoteric Acid in SH-SY5Y Cells and XIAP Interaction With Molecular Docking

Abstract

Gadoteric acid is a gadolinium-based contrast agent (GBCA) used to improve image quality in magnetic resonance imaging (MRI). Although it is also used in the diagnosis and prognosis of neuroblastoma, its effect on SH-SY5Y neuroblastoma cells remains unclear as a scientific gap. The aim of this study was to investigate the effects of gadoteric acid on cytogenotoxicity in SH-SY5Y neuroblastoma cells and its affinity with X-linked inhibitor of apoptosis (XIAP). After treatment of SH-SY5Y cells with gadoteric acid (0.1, 1, 10, and 100 mM), cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. After determining the IC50 value of gadoteric acid, the DNA damage effect of gadoteric acid (3.35, 6.7, 13.47, and 26.84 mM) on SH-SY5Y cells was investigated by Comet assay. Molecular docking analysis was carried out to identify the binding affinity of gadoteric acid to XIAP. Gadoteric acid (10 and 100 mM) significantly increased cytotoxicity in neuroblastoma cells (p < 0.0001 and p < 0.0001, respectively). Gadoteric acid (3.35, 6.7, 13.47, and 26.84 mM) caused a statistically significant increase in Genetic Damage Index (GDI) level in SH-SY5Y cells (p < 0.01, p < 0.05, p < 0.0001, and p < 0.001, respectively). Gadoteric acid (13.47 and 26.84 mM) also significantly increased the Damaged Cell Index (DCI) level in neuroblastoma cells (p < 0.01 and p < 0.01, respectively). The results of our study indicate that gadoteric acid used in MRI shows a cytogenotoxic effect on neuroblastoma cells and binds to XIAP with high affinity. These findings may provide insight into the use of gadoteric acid in the treatment of neuroblastoma and the molecular apoptosis mechanism of gadoteric acid.