Radiology Department, Faculty of Medicine, Firat University, Elazig, Turkey.
Physiology Department, Faculty of Medicine, Firat University, Elazig, Turkey.
J Cell Physiol. 2021 Mar;236(3):2139-2143. doi: 10.1002/jcp.30000. Epub 2020 Aug 1.
Contrast agents (CAs) used in magnetic resonance imaging (MRI) are produced by chelating the metal gadolinium (Gd) with organic ligand molecules to form stable complexes. But, Gd may dissociate from the CAs and subsequently might become toxic to its environment. Besides toxicity, it might inhibit calcium channels on cell membranes and this action could be detrimental to the cells governing biological development. The aim of this study was to investigate the interference of Gd3+ dechelated from the CAs by calcium signaling in the neuronal cells of gonadotropin-releasing hormone (GnRH), regulating puberty, and sexual development. The study used the mouse GT1-7 cell line as a model system, and Fura-2 based calcium imaging for detecting the interruption of intracellular calcium transport by the extracellular presence of Gd3+ as released from the CAs; gadodiamide and gadoterate meglumine, when the cells were stimulated in vitro culture by exposure to melatonin.The CA gadoterate meglumine interfered minimally with the calcium signaling, and thus its use is preferable in standard MRI exams. The release of Gd3+ from gadodiamide was significant and becomes of great concern as it may impact the neurophysiology of the neuronal cells in general, and gonadotropin production in particular, even in normal patients without nephrogenic systemic fibrosis. The toxicity induced by the influx of dechelated Gd3+ in the neurons of GnRH would have significant implications for puberty and reproductive functions.
磁共振成像（MRI）中使用的造影剂（CA）是通过螯合金属钆（Gd）与有机配体分子来形成稳定的配合物而产生的。但是，Gd 可能会从 CA 中解离出来，随后可能对其环境产生毒性。除了毒性之外，它还可能抑制细胞膜上的钙通道，这种作用可能对控制生物发育的细胞有害。本研究旨在研究从 CA 中脱螯合的 Gd3+通过钙信号对调节青春期和性发育的促性腺激素释放激素（GnRH）神经元细胞的干扰。该研究使用了小鼠 GT1-7 细胞系作为模型系统，并使用基于 Fura-2 的钙成像来检测细胞外存在的 Gd3+（从 CA 中释放）对细胞内钙转运的中断；当细胞在体外培养中受到褪黑素刺激时，使用造影剂 gadodiamide 和 gadoterate meglumine。CA gadoterate meglumine 对钙信号的干扰最小，因此在标准 MRI 检查中更可取。gadodiamide 释放的 Gd3+ 非常显著，引起了极大的关注，因为它可能会影响一般神经元细胞的神经生理学，特别是促性腺激素的产生，即使是在没有肾源性系统性纤维化的正常患者中也是如此。流入 GnRH 神经元的脱螯合 Gd3+ 引起的毒性会对青春期和生殖功能产生重大影响。
