Involvement of oxidative stress and mitochondrial/lysosomal cross-talk in olanzapine cytotoxicity in freshly isolated rat hepatocytes
Involvement of oxidative stress and mitochondrial/lysosomal cross-talk in olanzapine cytotoxicity in freshly isolated rat hepatocytes
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DOI：
10.3109/00498254.2015.1078522
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发表时间：
2016-01-01
期刊：
影响因子：
1.8
通讯作者：
Eghbal, Mohammad Ali
中科院分区：
文献类型：
--
作者：
Eftekhari, Aziz;Azarmi, Yadollah;Eghbal, Mohammad Ali
1.奥氮平（OLZ）是一种广泛使用的非典型抗精神病药物，用于治疗精神分裂症和其他疾病。在接受OLZ治疗的患者中报告了严重肝毒性和肝酶升高。然而，OLZ肝毒性的细胞和分子机制尚不清楚.在本研究中，评估了OLZ对新鲜分离的大鼠肝细胞的细胞毒性作用。我们的研究结果表明，OLZ在肝细胞中的细胞毒性是由活性氧（ROS）的过度产生，线粒体电位崩溃，溶酶体膜泄漏，GSH耗尽和脂质过氧化反应介导的细胞裂解前。所有上述OLZ诱导的细胞事件均显著（p
1. Olanzapine (OLZ) is a widely used atypical antipsychotic agent for the treatment of schizophrenia and other disorders. Serious hepatotoxicity and elevated liver enzymes have been reported in patients receiving OLZ. However, the cellular and molecular mechanisms of the OLZ hepatotoxicity are unknown.2. In this study, the cytotoxic effect of OLZ on freshly isolated rat hepatocytes was assessed. Our results showed that the cytotoxicity of OLZ in hepatocytes is mediated by overproduction of reactive oxygen species (ROS), mitochondrial potential collapse, lysosomal membrane leakiness, GSH depletion and lipid peroxidation preceding cell lysis. All the aforementioned OLZ-induced cellular events were significantly (p