Exploration in the cascade working mechanisms of liver injury induced by total saponins extracted from Rhizoma Dioscorea bulbifera

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• 作者：Fan Yang^a ; Yuqiong Liang^f ; Li Xu^a ; Leilei Ji^b ; Nan Yao^d ; ^e ; Ruonan Liu^c ; Le Shi^a ; ^{shilehappy@163.com" class="auth_mail" title="E-mail the corresponding author} ; Tao Liang^a ;
• 关键词：TSRD ; total saponins extracted from Rhizoma Dioscorea bulbifera ; DILI ; drug-induced liver injury ; DMEM ; Dulbecco&rsquo ; s modified Eagle medium ; FBS ; fetal bovine serum ; MTT ; 3-(4 ; 5-dimethylthiazol-2-yl) 2 ; 5-diphenyl tetrazolium bromide ; ALT ; alanine transaminase ; AST ; aspartate transaminase ; TBA ; total bile acid ; ALP ; alkaline phosphatase ; GLDH ; glutamate dehydrogenase ; ELISA ; enzyme-linked immunosorbent assay ; SOD ; superoxide dismutase ; MDA ; metahne dicarboxylic aldehyde ; GSH-PX ; glutathione pe
• 刊名：Biomedicine & Pharmacotherapy
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：83
• 期：Complete
• 页码：1048-1056
• 全文大小：3647 K

文摘

Rhizoma Dioscorea bulbifera, the tuber of Dioscorea bulbifera L., has been used to treat various diseases. However, the clinical application has been limited for its hepatotoxicity. In this study, we explored the cascade working mechanisms of time-dependent hepatotoxicity induced by total saponins extracted from Rhizoma Dioscorea bulbifera (TSRD). Animals were orally administered with TSRD for indicated time period. The adverse effects were determined by histopathology and biochemistry. Similar hepatic index was analyzed in L-O2 cells exposed to dioscin for different durations. We found that TSRD could initially cause cell damage and cholestasis in rats. With the treatment going on, oxidative stress injury and up-regulation of Cytochromes P450 (CYPs) were observed both in vitro and in vivo. Eventually, TSRD induced mitochondrial permeability results in apoptosis or necrosis. Taken together, we provided evidence for the time-dependent hepatotoxicity of TSRD and created a 3-step injury model to clarify its cascade working mechanisms.