The role of glutathione in the toxicity of a novel cyanobacterial alkaloid cylindrospermopsin in cultured rat hepatocytes.
The role of glutathione in the toxicity of a novel cyanobacterial alkaloid cylindrospermopsin in cultured rat hepatocytes.
复制标题
谷胱甘肽在培养大鼠肝细胞中新型蓝藻生物碱圆柱精蛋白的毒性中的作用。
DOI：
10.1006/bbrc.1994.1694
复制
发表时间：
1994
影响因子：
3.1
通讯作者：
Lu,SC
中科院分区：
文献类型：
--
作者：
Runnegar,MT;Kong,SM;Zhong,YZ;Ge,JL;Lu,SC
草菇素（acidrospermopsin，CY）是一种新分离的由草菇蓝细菌（acidrospermopsis raciborskii）产生的生物碱，它与人类暴发性肝肠炎有关，本工作探讨了原代培养大鼠肝细胞作为CY细胞毒性体外研究模型的适宜性。我们发现，CY（3.3-5.0 μM）孵育18小时后，在培养的肝细胞中引起显著的细胞死亡（40-67%的细胞释放LDH）。在研究CY毒性的可能机制时，我们发现较低的无毒剂量的CY（1.6-2.5 μM）使细胞谷胱甘肽（GSH）降低至对照组的约50%。对于毒性剂量（5 μM），GSH的损失先于毒性发作6小时。降低细胞GSH使细胞易于产生CY毒性。总之，培养的肝细胞是一个合适的模型，CY细胞毒性的研究和GSH参与的CY的解毒。
Cylindrospermopsin (CY) is a newly isolated alkaloid produced by the cyanobacteriumCylindrospermopsis raciborskii, which has been linked to an outbreak of hepatoenteritis in man. The current work examined the suitability of primary cultures of rat hepatocytes as anin vitromodel for studying the cytotoxicity of CY. We found that CY (3.3-5.0 μM) caused significant cell death (40-67% of cells by LDH release) in cultured hepatocytes after 18 hr incubation. While investigating possible mechanisms for CY toxicity, we found that lower, nontoxic doses of CY (1.6-2.5 μM) decreased cell glutathione (GSH) to about 50% of control. For toxic doses (5 μM), the loss of GSH preceded the onset of toxicity by six hr. Lowering cell GSH predisposed cells to CY toxicity. In conclusion, cultured hepatocytes are a suitable model for studies of CY cytotoxicity and GSH is involved in the detoxification of CY.