Utilization of electron probe microanalysis in gadolinium-treated mice

Area of Science:

• Toxicology
• Cell Biology
• Medical Imaging

Background:

• Gadolinium (Gd) compounds are used as contrast agents in magnetic resonance imaging (MRI).
• Gd is also studied experimentally for its ability to block Kupffer cell phagocytosis.
• Understanding Gd's subcellular distribution is crucial for assessing its toxicological profile.

Purpose of the Study:

• To determine the subcellular localization of gadolinium chloride (GdCl3) in mice.
• To investigate the toxicological effects of short-term GdCl3 administration.
• To evaluate the utility of electron probe microanalysis in Gd toxicology.

Main Methods:

• Mice were administered varying doses of GdCl3 intravenously for 14 days.
• Liver-associated enzymes were measured, and liver histology was examined.
• Morphological investigations of cellular injury were performed on high-dose animals.
• Electron probe microanalysis was used to identify the subcellular localization of gadolinium.

Main Results:

• Elevated liver enzymes and hepatocellular degeneration were observed in high-dose mice.
• Cellular injury, including swollen mitochondria and vesiculated endoplasmic reticulum, was noted in hepatocytes and Kupffer cells.
• Discrete, electron-dense granular material, confirmed as gadolinium, was found intracellularly in liver, lung, spleen, and kidney cells.
• Gadolinium accumulated in hepatocytes, Kupffer cells, bile canaliculi, neutrophils, pulmonary interstitial macrophages, splenic macrophages, and renal mesangial cells.

Conclusions:

• Gadolinium chloride administration leads to both hepatic and extra-hepatic accumulation.
• Cells of the mononuclear phagocytic system are significant sites of gadolinium accumulation.
• Electron probe microanalysis is a valuable tool for assessing the toxicologic distribution of gadolinium.