Cerebral Accumulation of Gadolinium (Gd³⁺) and Related Cellular Stress Pathways in Rat Brain Tissue

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).

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.

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.

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.