Intracellular Penetration and Accumulation of Radiographic Contrast Media in the Rat Kidney

Radiographic iodine-containing contrast media (meglumine calcium metrizoate, iohexol and meglumine sodium ioxaglate) were injected intravenously in rats. At various intervals after exposure, in situ cryofixation of kidneys was performed. Thin, freeze-dried cryosections were examined by electron microscopy and X-ray microanalysis. In endothelial cells, erythrocytes and tubular cells high dry weight concentrations of iodine were found. Twenty-four hours after iohexol was injected, no trace of iodine was found in the plasma, microvilli or the nuclei of the tubular cells. Small organelle-like compartments in the cytoplasm of the proximal tubular cells contained high concentrations of iodine, whereas no iodine was found in the surrounding cytoplasm. Since no metabolism of contrast medium has been demonstrated, the iodine signals must be emitted from contrast medium molecules. Other elements were also measured, with the concentrations being always within the ranges found in tubular cells of control animals. The detection of intracellular contrast thus does not seem to be an artifact due to cell injury, but rather represents a physiological event in healthy cells in the rat kidney. Our results are in contradiction to the prevailing opinion that contrast media do not enter healthy cells. However, previous conclusions have been based on the use of conventional preparation methods, and the highly water soluble contrast molecules may have been lost during the different steps of fixation and processing