In vitro model of the human liver parenchyma to study hepatotoxic side effects by Dy-EOB-DTPA.

摘要

RATIONALE AND OBJECTIVES: In vivo studies have shown species-specific toxicity after application of the liver-specific contrast agent Dy-ethoxybenzyl (EOB)-DTPA. To predict species differences in the laboratory, an in vitro model of the liver was used to examine the divergent results. METHODS: Rat, canine, porcine, and human hepatocytes were isolated and embedded between layers of collagen. During and after 48 hours of incubation with different concentrations of Dy-EOB-DTPA (maximum concentration 50 mmol/L), morphological changes and enzyme leakage were determined. RESULTS: The response to the contrast agent varied for hepatocytes from different species. For canine cells, morphological changes and cell death were evident with as little as 5 mmol/L Dy-EOB-DTPA. Rat hepatocytes tolerated up to 50 mmol/L Dy-EOB-DTPA, and enzyme leakage was transient. Only after incubation with 50 mmol/L Dy-EOB-DTPA was the formation of intracellular vacuoles evident. In contrast, even the highest concentration of Dy-EOB-DTPA did not cause an enzyme leakage of porcine or human hepatocytes, although similar vacuoles were seen. CONCLUSIONS: These data demonstrate a species-dependent toxicity for Dy-EOB-DTPA in vitro, with similar responses in porcine and human hepatocytes.