title: Role of Nrf2 in protection against triptolide-induced toxicity in rat kidney cells.
abstract: Triptolide is a major active ingredient of the Chinese herb Tripterygium wilfordii Hook f. (TWHF) and has been shown to possess multiple biological activities, such as anti-inflammatory, anti-fertility, anti-neoplastic and immunosuppressive activities. However, severe adverse effects, especially nephrotoxicity, limit its clinical use. Oxidative stress has been reported to be involved in triptolide-induced renal injury, but the existence of other mechanisms remains unclear. This study aimed to investigate whether NF-E2-related factor 2 (Nrf2), which is an antioxidant nuclear transcription factor, plays a protective role in defense against triptolide-induced toxicity in a normal rat kidney cell line (NRK-52E). Triptolide induced oxidative stress in NRK-52E cells by induction of reactive oxygen species (ROS) and depletion of glutathione (GSH), which resulted in a rapid increase in Nrf2 nuclear accumulation, as well as an induction of antioxidant response element (ARE)-driven genes. In addition, overexpression of Nrf2 protected against triptolide-induced cell death, whereas knockdown of Nrf2 by its specific small interfering RNA resulted in increased cytotoxicity. We also found that Nrf2 knockdown enhanced both the production of ROS and the depletion of GSH. Taken together, these results indicate that activation of Nrf2 plays a protective role against triptolide-induced cytotoxicity in NRK-52E cells through the counteraction of oxidative stress.
authors: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, PR China.
authors: Jia
authors: J
authors: Li
authors: Jing
authors: J
authors: Jin
authors: Mei
authors: M
authors: Li
authors: Cuiwen
authors: C
authors: Guan
authors: Wenwen
authors: W
authors: Wang
authors: Shaohua
authors: S
authors: Zhu
authors: Yuwen
authors: Y
authors: Qiu
authors: Min
authors: M
authors: Huang
authors: Zhiying
authors: Z
authors: Huang
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000633:toxicity; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004224:Diterpenes / Q000633:toxicity*; D004852:Epoxy Compounds / Q000633:toxicity; D005978:Glutathione / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism* / Q000648:ultrastructure; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008858:Microscopy, Phase-Contrast; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D010616:Phenanthrenes / Q000633:toxicity*; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D018906:Antineoplastic Agents, Alkylating; D004224:Diterpenes; D004852:Epoxy Compounds; D051267:NF-E2-Related Factor 2; D010616:Phenanthrenes; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; C001899:triptolide; D007770:L-Lactate Dehydrogenase; D005978:Glutathione