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Time Course of Stomach Mineralization, Plasma, and Urinary Changes After a Single Intravenous Administration of Gadolinium(III) Chloride in the Male Rat

Sanofi Research, Alnwick Research Centre, Willowburn Avenue, Alnwick, Northumberland NE66 2JH, United Kingdom

Andrew Spencer

Sanofi Research, Alnwick Research Centre, Willowburn Avenue, Alnwick, Northumberland NE66 2JH, United Kingdom

Susan Wilson

Sanofi Research, Alnwick Research Centre, Willowburn Avenue, Alnwick, Northumberland NE66 2JH, United Kingdom

Alexandra Reid

Sanofi Research, Alnwick Research Centre, Willowburn Avenue, Alnwick, Northumberland NE66 2JH, United Kingdom

Ernest Harpur

Sanofi Research, Alnwick Research Centre, Willowburn Avenue, Alnwick, Northumberland NE66 2JH, United Kingdom

In a previous experiment it was reported that the intravenous administration of gadolinium chloride (GdCl,) to rats results in a discrete band of interstitial mineralization in the fundic glandular mucosa of the stomach. To investigate the time course for the development of this lesion and its relationship to plasma calcium and phosphate concentrations, 2 experiments were carried out in male Sprague-Dawley rats given a single intravenous dose of 0.07 mmol/kg GdCl,. Plasma calcium and phosphate concentrations approximately doubled between 30 min and 12 hr postdose but had regressed back to near normal values by 24 hr. However, there were no observable clinical signs in treated animals. Histologically, there was progressive mineralization of the lamina propria of the neck region of the fundic glands from 6 hr postdose, forming a distinctive mineral band by 12 hr postdose. At 7 and 14 days postdose the mineral deposits were accompanied by mucous cell hyperplasia, interstitial fibrosis, and a very sparse infiltration of inflammatory cells. By 56 days postdose only occasional mineral deposits remained. Transmission electron microscopy showed mineral first nucleated on collagen in the interstitium, but there was no evidence of cell necrosis. X-ray microanalysis showed that the interstitial mineral was composed of calcium and phosphate in the form of hydroxyapatite; gadolinium (Gd) was only very rarely identified. These findings are consistent with metastatic mineralization. The source, cause, and the exact nature of the excess plasma calcium and phosphate are unknown, and the possible significance of this effect for clinical use of Gd-containing chelates in nuclear magnetic resonance imaging requires further investigation.

Key Words: X-ray microanalysis • hypercalcemia • hyperphosphatemia • calcification • mucous cell hyperplasia

Toxicologic Pathology, Vol. 25, No. 6, 582-589 (1997)
DOI: 10.1177/019262339702500607


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