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

RATIONALE AND OBJECTIVES. In vivo studies have shown species-specific toxic ity after application of the liver-specific contrast agent Dy-ethoxybenzyl (EOB)-DTPA, To predict species differences in the laboratory, an in vitro m odel of the liver was used to examine the divergent results. METHODS. Rat, canine, porcine, and human hepatocytes were isolated and embe dded between layers of collagen. During and after 48 hours of incubation wi th 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 dif ferent 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 i ncubation with 50 mmol/L Dy-EOB-DTPA was the formation of intracellular vac uoles evident. In contrast, even the highest concentration of Dy-EOB-DTPA d id not cause an enzyme leakage of porcine or human hepatocytes, although si milar 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.