Department of Zoology, University of Pune, Pune 411 007, India.
Fitoterapia. 2012 Dec;83(8):1562-8. doi: 10.1016/j.fitote.2012.09.003. Epub 2012 Sep 13.
Ethanol mediated free radical generation plays an important role in the pathogenesis of liver injuries and alcoholic liver diseases. In the present study two ellagitannins namely geraniin and amariin isolated from Phyllanthus amarus were examined for their ability to protect mouse liver slices against ethanol induced toxicity and possible mechanism of its protection. Oxidative stress markers such as, lipid peroxidation, protein carbonyl formation, amount of 8-hydroxy-2-deoxyguanosine and antioxidant enzymes levels were measured using specific biochemical assays. Poly (ADP-ribose) polymerase (PARP), Bax and Bcl2 were checked to assess the induction of apoptosis using western blots. The results showed that geraniin and amariin protected mouse liver slices against ethanol induced cytotoxicity. Both compounds inhibited oxidation of lipid, protein and formation of 8-hydroxy-2-deoxyguanosine, all of which were found to be elevated on exposure to ethanol. These compounds restored the antioxidant enzymes altered on ethanol exposure. Compounds also inhibited the cleavage of PARP and bax and restored Bcl2, induced on exposure to ethanol. In summary, both ellagitannins effectively protected mouse liver slices against ethanol induced cytotoxicity and apoptosis by reducing oxidative damage to biological molecules and modulating Bax/Bcl-2 ratio respectively, thus minimizing liver injury.
乙醇介导的自由基生成在肝损伤和酒精性肝病的发病机制中起着重要作用。在本研究中,从叶下珠中分离得到的两种鞣花单宁即石榴素和安石榴苷,研究了它们保护小鼠肝切片免受乙醇诱导的毒性的能力及其可能的保护机制。使用特定的生化测定法测量氧化应激标志物,如脂质过氧化、蛋白质羰基形成、8-羟基-2-脱氧鸟苷的量和抗氧化酶水平。使用 Western blot 检查多聚(ADP-核糖)聚合酶(PARP)、Bax 和 Bcl2,以评估细胞凋亡的诱导。结果表明,石榴素和安石榴苷可保护小鼠肝切片免受乙醇诱导的细胞毒性。两种化合物均抑制脂质、蛋白质氧化和 8-羟基-2-脱氧鸟苷的形成,这些在接触乙醇时均升高。这些化合物恢复了暴露于乙醇时改变的抗氧化酶。化合物还抑制了 PARP 和 bax 的裂解,并恢复了 Bcl2,这是暴露于乙醇时诱导的。总之,两种鞣花单宁通过减少生物分子的氧化损伤和分别调节 Bax/Bcl-2 比值,有效保护小鼠肝切片免受乙醇诱导的细胞毒性和凋亡,从而最小化肝损伤。