Triptriolide antagonizes triptolide-induced nephrocyte apoptosis via inhibiting oxidative stress in vitro and in vivo
Autor: | Peng Xu, Tian Ruimin, Wei Mao, Hongtao Xu, Bo Liu, Yang Yiqi, Han Xiaodong, Zhao-Yu Lu, Xusheng Liu, Xiao-wan Wang |
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Rok vydání: | 2019 |
Předmět: |
Male
0301 basic medicine Cell Survival NF-E2-Related Factor 2 Apoptosis RM1-950 Pharmacology Kidney Cell morphology medicine.disease_cause Cell Line Superoxide dismutase 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine In vivo medicine Animals Humans Cell Shape chemistry.chemical_classification Mice Inbred BALB C Reactive oxygen species Triptolide biology Chemistry Nrf2 pathway General Medicine Phenanthrenes Heme oxygenase Oxidative Stress 030104 developmental biology 030220 oncology & carcinogenesis biology.protein Epoxy Compounds Therapeutics. Pharmacology Diterpenes Triptriolide Oxidative stress Signal Transduction |
Zdroj: | Biomedicine & Pharmacotherapy, Vol 118, Iss, Pp-(2019) |
ISSN: | 0753-3322 |
DOI: | 10.1016/j.biopha.2019.109232 |
Popis: | Triptolide(T9) is a predominant bioactive component extracted from Chinese herb Tripterygium wilfordii Hook F. (TwHF), and has multiple pharmacological activities, such as immunosuppressive and anti-inflammatory activities, et al. However, severe adverse effects and toxicity, particularly nephrotoxicity, limit its clinical application. It has been demonstrated that the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway could alleviate T9-induced nephrocyte damage. The aim of this study was to investigate the potential protective role of triptriolide (T11) against T9-induced nephrocyte apoptosis in vitro and in vivo. Renal injury models were established in human kidney 2 (HK2) cells and BALB/c mice using T9, and the protective effects of T11 were probed in vitro and in vivo, respectively. T9 induced nephrocyte damage in HK2 cells and BALB/c mice by induction of reactive oxygen species (ROS), lactate dehydrogenase (LDH), malondialdehyde (MDA) and glutathione (GSH) and reduction of superoxide dismutase (SOD), which resulted in the apoptosis of nephrocyte and injury of renal function. While, pretreatment of T11 effectively reversed these changes, resulting in the obvious decrease of oxidative stress and renal function parameters, ameliorated nephrocyte apoptosis, improved cell morphology, and higher increase of Nrf2, NAD(P)H: quinine oxidoreductase 1 (NQO1) and heme oxygenase 1 (HO-1) protein levels in vitro and in vivo. Altogether, T11 protected against T9-induced nephrocyte apoptosis possibly via suppressing oxidative stress. |
Databáze: | OpenAIRE |
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