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Cerebral Accumulation of Gadolinium (Gd3+) and Related Cellular Stress Pathways in Rat Brain Tissue
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DOI：10.3390/tomography12030037.png)
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Abstract
En 中文
Background/Objectives: This study aimed to compare in vivo cerebral gadolinium (Gd3+) accumulation, associated unfolded protein response (UPR), and oxidative stress parameters in rats after exposure to gadolinium-based contrast agents (GBCAs). Methods: This study was designed as a controlled, experimental animal study to evaluate the accumulation of Gd3+ in the basal ganglia of rats following the administration of 0.6 mmol/kg gadopentetate dimeglumine (linear) and gadoterate meglumine (macrocyclic). Male Sprague-Dawley rats were exposed to the contrast agents for 24 and 72 h, and then the basal ganglia tissues were collected postmortem. The tissue levels of Gd3+ accumulation, activating transcription factor-6 (ATF6), inositol-requiring enzyme-1 (IRE-1), protein kinase RNA-like endoplasmic reticulum kinase (PERK), damage-inducible transcript-3 (DDIT3), total antioxidant status (TAS), and total oxidant status (TOS) were determined. Results: Linear GBCA-treated rats had persistent Gd3+ levels over time, whereas a significant reduction from 24 to 72 h was observed in macrocyclic GBCA-treated rats (p < 0.001). PERK, DDIT3, and ATF6 expressions were significantly elevated after linear GBCA exposure (p < 0.05), while no significant increase was observed in the macrocyclic GBCA-treated group. However, IRE-1, TAS, and TOS levels were not significantly different in either group. Conclusions: Linear and macrocyclic GBCAs demonstrated distinct patterns of cerebral Gd3+ accumulation and UPR levels in rats. Accordingly, GBCA administration should be reserved for instances where it is necessary, such as when contrast enhancement is clinically required.
Keywords:
gadolinium-based contrast agents
cerebral gadolinium accumulation
unfolded protein response
oxidative stress
rat model
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