Lee Kyung Jin, Choi Chul Yung, Chung Young Chul, Kim Young Sup, Ryu Si Yung, Roh Seong Hwan, Jeong Hye Gwang
Department of Pharmacy, College of Pharmacy, Chosun University, 375 Seosuk-dong, Kwangju 501-759, South Korea.
Toxicol Lett. 2004 Mar 7;147(3):271-82. doi: 10.1016/j.toxlet.2003.12.002.
There is increasing evidence that oxidative stress is implicated in the pathogenesis of various diseases, including alcoholic liver injury. In the present work, we investigate the protective effects of the saponins isolated from the roots of Platycodon grandiflorum A. DC (Campanulaceae), Changkil saponins (CKS), on the tert-butyl hydroperoxide (t-BHP)-induced oxidative injury (hepatotoxicity) in cultured rat primary hepatocytes and in rat livers. CKS significantly reduced t-BHP-induced oxidative injuries in cultured rat hepatocytes, as determined by cell cytotoxicity, intracellular glutathione (GSH) content and lipid peroxidation in a dose-dependent manner. CKS provided good protection from the t-BHP-induced production of intracellular reactive oxygen species and DNA damage. In addition, CKS was able to quench 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radicals and the superoxide radical. The in vivo study showed that the pretreatment with CKS prior to the administration of t-BHP significantly prevented the increase in the serum levels of hepatic enzyme markers (alanine aminotransferase and aspartate aminotransferase) and reduced oxidative stress, such as GSH content and lipid peroxidation, in the liver in a dose-dependent manner. These results support the anti-oxidative role of CKS, and demonstrate that CKS can scavenge oxygen free radicals and protect cells from oxidative stress.
越来越多的证据表明,氧化应激与包括酒精性肝损伤在内的各种疾病的发病机制有关。在本研究中,我们研究了从桔梗(桔梗科)根部分离出的皂苷——常吉皂苷(CKS)对叔丁基过氧化氢(t-BHP)诱导的原代培养大鼠肝细胞和大鼠肝脏氧化损伤(肝毒性)的保护作用。通过细胞毒性、细胞内谷胱甘肽(GSH)含量和脂质过氧化作用测定,CKS能以剂量依赖的方式显著减轻t-BHP诱导的原代培养大鼠肝细胞氧化损伤。CKS能有效保护细胞免受t-BHP诱导的细胞内活性氧生成和DNA损伤。此外,CKS能够淬灭1,1-二苯基-2-苦基肼(DPPH)自由基和超氧阴离子自由基。体内研究表明,在给予t-BHP之前用CKS预处理能显著预防肝酶标志物(丙氨酸转氨酶和天冬氨酸转氨酶)血清水平的升高,并以剂量依赖的方式减轻肝脏中的氧化应激,如GSH含量和脂质过氧化。这些结果支持了CKS的抗氧化作用,并证明CKS可以清除氧自由基并保护细胞免受氧化应激。