title: Protective effect of Wuzhi tablet (Schisandra sphenanthera extract) against cisplatin-induced nephrotoxicity via Nrf2-mediated defense response.
abstract: Cisplatin is a potent anti-cancer agent for various types of tumors. However, the clinical use of cisplatin is often limited by its nephrotoxicity. This study reports that WZ tablet (WZ, a preparation of an ethanol extract of Schisandra sphenanthera) mitigates cisplatin-induced toxicity in renal epithelial HK-2 cells and in mice. Pretreatment of HK-2 cells with WZ ameliorated cisplatin-induced cytotoxicity caused by oxidative stress, as was demonstrated by reductions in the levels of reactive oxygen species (ROS) and increased levels of glutathione (GSH). WZ facilitated the nuclear accumulation of the transcription factor NF-E2-related factor 2 (Nrf2) and the subsequent expression of its target genes such as
  quinine oxidoreductase 1 (NQO1), heme oxygenase-1 (HO-1) and glutamate cysteine ligase (GCL). Protective effects of WZ on cisplatin-induced nephrotoxicity were also observed in mice. WZ attenuated cisplatin-induced renal dysfunction, structural damage and oxidative stress. The nuclear accumulation of Nrf2 and its target genes were increased by WZ treatment. Taken together, these findings demonstrated WZ have a protective effect against cisplatin-induced nephrotoxicity by activation of the Nrf2 mediated defense response, which is of significant importance for therapeutic intervention in cisplatin induced renal injury.
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, 132 East Circle at University City, Guangzhou 510006, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Jin
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, 132 East Circle at University City, Guangzhou 510006, PR China.
authors.forename: Mei
authors.initials: M
authors.lastname: Li
authors.affiliation: School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China.
authors.forename: Zhongxiang
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, 132 East Circle at University City, Guangzhou 510006, PR China.
authors.forename: Xiaozhe
authors.initials: X
authors.lastname: Sun
authors.affiliation: Pharmaceutical Department, Cancer Center of Guangzhou Medical University, Guangzhou 510095, PR China.
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, 132 East Circle at University City, Guangzhou 510006, PR China.
authors.forename: Wenwen
authors.initials: W
authors.lastname: Wang
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, 132 East Circle at University City, Guangzhou 510006, PR China.
authors.forename: Min
authors.initials: M
authors.lastname: Huang
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, 132 East Circle at University City, Guangzhou 510006, PR China. Electronic address: hzhiying@mail.sysu.edu.cn.
authors.forename: Zhiying
authors.initials: Z
authors.lastname: Huang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects; D002460:Cell Line; D002945:Cisplatin / Q000009:adverse effects*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005721:Glutamate-Cysteine Ligase / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced; D015227:Lipid Peroxidation; D008297:Male; D051379:Mice; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D032141:Schisandra / Q000737:chemistry; D013607:Tablets
chemical_list: D000970:Antineoplastic Agents; D004365:Drugs, Chinese Herbal; D051267:NF-E2-Related Factor 2; D017382:Reactive Oxygen Species; D013607:Tablets; C582515:wuzhi; D051547:Heme Oxygenase-1; D016660:NAD(P)H Dehydrogenase (Quinone); D005721:Glutamate-Cysteine Ligase; D005978:Glutathione; D002945:Cisplatin
keywords: Cisplatin; Nephrotoxicity; Nrf2; Schisandra sphenanthera; Wuzhi tablet