From the Department of Anesthesiology and Intensive Care Medicine, University Hospital of Rostock (MS, IP, CH, GR, GN-S, TM); and Fraunhofer Institut for Cell Therapy and Immunology, Project Group EXIM, Rostock, Germany (MS, MM).
Eur J Anaesthesiol. 2017 Sep;34(9):623-627. doi: 10.1097/EJA.0000000000000666.
The development of liver failure is a major problem in critically ill patients. The hepatotoxicity of many drugs, as one important reason for liver failure, is poorly screened for in human models. Rocuronium and succinylcholine are neuromuscular blocking agents used for tracheal intubation and for rapid-sequence induction.
We used an in-vitro test with a permanent cell line and compared rocuronium and succinylcholine for hepatotoxicity.
In-vitro study.
A basic science laboratory, University Hospital Rostock, Germany.
MATERIAL/(PATIENTS): The basic test compound is the permanent human liver cell line HepG2/C3A. In a standardised microtitre plate assay the toxicity of different concentrations of rocuronium, succinylcholine and plasma control was tested.
After two incubation periods of 3 days, the viability of cells (XTT test, lactate dehydrogenase release and trypan blue staining), micro-albumin synthesis and the cytochrome 1A2 activity (metabolism of ethoxyresorufin) were measured.
Differences between rocuronium and succinylcholine were assessed using the Kruskal-Wallis one-way test and two-tailed Mann-Whitney U test.
Rocuronium, but not succinylcholine, led to a significant dose-dependent decrease of viability, albumin synthesis and cytochrome 1A2 activity of test cells.
An in-vitro test with a cell line showed hepatotoxicity of rocuronium that was dose-dependent. Further studies are needed to investigate the underlying mechanisms of the effects of rocuronium on hepatic cellular integrity.
Not suitable.
肝功能衰竭是危重病患者的一个主要问题。许多药物的肝毒性是导致肝功能衰竭的一个重要原因，但在人体模型中对其进行筛选的效果不佳。罗库溴铵和顺式阿曲库铵是用于气管插管和快速序贯诱导的神经肌肉阻滞剂。
我们使用一种具有永久细胞系的体外试验，比较了罗库溴铵和顺式阿曲库铵的肝毒性。
体外研究。
德国罗斯托克大学医院基础科学实验室。
材料/（患者）：基本测试化合物是永久人肝细胞系 HepG2/C3A。在标准化微量板测定中，测试了不同浓度的罗库溴铵、顺式阿曲库铵和血浆对照的毒性。
在 3 天的两个孵育期后，通过 XTT 试验、乳酸脱氢酶释放和台盼蓝染色测量细胞活力（细胞活力）、微量白蛋白合成和细胞色素 1A2 活性（乙氧基Resorufin 的代谢）。
使用 Kruskal-Wallis 单向检验和双侧曼-惠特尼 U 检验评估罗库溴铵和顺式阿曲库铵之间的差异。
罗库溴铵而非顺式阿曲库铵导致测试细胞的活力、白蛋白合成和细胞色素 1A2 活性呈剂量依赖性显著下降。
细胞系的体外试验显示罗库溴铵具有剂量依赖性的肝毒性。需要进一步研究以探讨罗库溴铵对肝细胞完整性的影响的潜在机制。
不适用。
