Division of Molecular Medicine, Bose Institute, Kolkata, India.
Toxicol In Vitro. 2010 Sep;24(6):1711-9. doi: 10.1016/j.tiv.2010.05.014. Epub 2010 May 25.
The present study has been designed and carried out to investigate the mechanism of the protective action of a novel antioxidant protein molecule, isolated from the herb, Phyllanthus niruri (PNP), against tertiary butyl hydroperoxide (TBHP) induced cytotoxicity and cell death. Incubation of hepatocytes with PNP prevented TBHP-induced loss in cell viability and enhanced LDH leakage in a dose-dependent manner. Reduction in GSH/GSSG ratio and activities of antioxidant enzymes have also been found to be prevented by this protein. Moreover, TBHP exposure caused injury in cellular mitochondria, disrupted mitochondrial membrane potential, induced reciprocal regulation of Bcl-2 family proteins and facilitated cytochrome c release in the cytosol. In addition, TBHP introduces apoptosis as the primary phenomena of cell death as evidenced by DAPI staining, flow cytometric analyses and studies on the activation of caspases. PNP treatment, however, counteracted these changes and maintains normalcy in hepatocytes. Combining, data suggest that PNP possesses cytoprotective activity against TBHP-induced oxidative cellular damage and prevents hepatocytes from apoptotic death.
本研究旨在探讨从草药叶下珠（PNP）中分离出的新型抗氧化蛋白分子对叔丁基过氧化物（TBHP）诱导的细胞毒性和细胞死亡的保护作用机制。PNP 孵育可防止肝细胞 TBHP 诱导的活力丧失，并呈剂量依赖性增强 LDH 漏出。这种蛋白还可以防止 GSH/GSSG 比和抗氧化酶活性的降低。此外，TBHP 暴露会导致细胞线粒体损伤，破坏线粒体膜电位，诱导 Bcl-2 家族蛋白的相互调节，并促进细胞色素 c 向细胞质释放。此外，TBHP 将细胞凋亡作为细胞死亡的主要现象引入，这可以通过 DAPI 染色、流式细胞术分析以及对 caspase 激活的研究来证明。然而，PNP 处理可以对抗这些变化，使肝细胞保持正常。综合数据表明，PNP 具有对抗 TBHP 诱导的氧化细胞损伤的细胞保护活性，并防止肝细胞发生凋亡性死亡。
