Sorensen E M, Acosta D
Drug Chem Toxicol. 1985;8(4):219-37. doi: 10.3109/01480548509038647.
Using primary cultures of parenchymal hepatocytes as a model system, the cytotoxic potential of dantrolene sodium (DS) was compared with that of erythromycin estolate (EE)--a known hepatotoxin. Parallel morphological and functional comparisons were made, following 4-, 8-, or 24-h exposures of hepatocyte cultures, using phase contrast microscopy and lactate dehydrogenase (LDH) leakage, respectively. Four-hour exposures of cultures to rather low concentrations of EE (i.e. 50 microM) resulted in cellular necrosis and significantly elevated LDH release. As the concentration of this hepatotoxin was increased, the changes were more pronounced. However, even 4- or 8-h exposures of cultures to a maximum of 100 microM DS did not affect LDH leakage or morphological integrity, although marginally detectable morphological changes did not occur at the highest concentration after 24-h. The value of using primary parenchymal hepatocyte cultures as a model system for the assessment of xenobiotic-induced hepatotoxicity was confirmed.
以原代培养的实质肝细胞作为模型系统，比较了丹曲林钠（DS）与已知肝毒素依托红霉素（EE）的细胞毒性潜力。在肝细胞培养物分别暴露4小时、8小时或24小时后，使用相差显微镜和乳酸脱氢酶（LDH）泄漏进行了平行的形态学和功能比较。培养物暴露于相当低浓度的EE（即50微摩尔）4小时导致细胞坏死，并显著提高LDH释放。随着这种肝毒素浓度的增加，变化更加明显。然而，即使培养物暴露于最高100微摩尔的DS 4小时或8小时，也不会影响LDH泄漏或形态完整性，尽管在24小时后最高浓度下出现了轻微可检测的形态变化。证实了使用原代实质肝细胞培养物作为评估外源化合物诱导的肝毒性的模型系统的价值。
