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学科主题: 公共卫生
题名:
Differential cytotoxic effects of denitroaristolochic acid II and aristolochic acids on renal epithelial cells
作者: Liu, Qing1; Wang, Qi1; Yang, Xiuwei2; Shen, Xiaofan1; Zhang, Baoxu1
关键词: Denitroaristolochic acid ; MDCK cells ; Cytotoxicity ; Reactive oxygen species (ROS)
刊名: TOXICOLOGY LETTERS
发表日期: 2009-01-10
DOI: 10.1016/j.toxlet.2008.10.020
卷: 184, 期:1, 页:5-12
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Toxicology
研究领域[WOS]: Toxicology
关键词[WOS]: TUBULAR CELLS ; METABOLIC-ACTIVATION ; APOPTOSIS ; KIDNEY ; NEPHROTOXICITY ; NEPHROPATHY ; INDUCTION ; CYTOMETRY ; CHLORIDE ; MERCURY
英文摘要:

Aristolochic acids (AAs), naturally occurring nephrotoxins and rodent carcinogens, are commonly found in medicinal plants such as Radix atistolochiae. The toxicity of AAs is believed to be associated with the formation of promutagenic AA-DNA adducts, and it has also been suggested that the nitro group in AAs might be important in the process. In order to investigate the role of the nitro group in AA-mediated cytotoxicity, the effects of denitroaristolochic acid II (dN-AAII), aristolochic acid 11 (AAII) and aristolochic acid I (AAI) on renal tubular epithelial Madin-Darby canine kidney (MDCK) cells were examined and compared. The cytotoxicity of AAI, AAII and dN-AAII was found to be time- and concentration-dependent. As determined by MTT assay, AAI was found to be most toxic in MDCK cells upon exposure for 24, 48 and 72 h. followed by AAII, and dN-AAII showed the least cytotoxicity. The effect of AAI and AAII on the integrity of cell membrane was found to be similar and appeared to be more prominent than that of dN-AAII Based on the results obtained from the flow cytometric analysis, significant apoptosis in MDCK cells was observed with AAI and AAII at as low as 25 mu mol/L following exposure for 24 h, whereas significant apoptosis was induced by dN-AAII at a much higher concentration, 300 mu mol/L, suggesting that both AAI and AAII were significantly more cytotoxic than dN-AAII In addition, the levels of reactive oxygen species (ROS) were increased following treatment with AAI, AAII and dN-AAII at concentrations of 5, 25 and 25 mu mol/L, respectively, for 4 h. The results suggest that the nitro group plays an important role in AA-mediated cytotoxicity in MDCK cells and increased intracellular ROS levels may be associated, at least in part, with the cell injury observed in MDCK cells. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

语种: 英语
所属项目编号: 2002AA2Z343C ; 2004AA2Z3730-07 ; Z0004105040311
项目资助者: National High Technology Program of China ; Committee of Science and Technology of Beijing, PR China
WOS记录号: WOS:000262544400002
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/67003
Appears in Collections:北京大学公共卫生学院_期刊论文

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作者单位: 1.Peking Univ, Sch Publ Hlth, Beijing 100083, Peoples R China
2.Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing 100083, Peoples R China

Recommended Citation:
Liu, Qing,Wang, Qi,Yang, Xiuwei,et al. Differential cytotoxic effects of denitroaristolochic acid II and aristolochic acids on renal epithelial cells[J]. TOXICOLOGY LETTERS,2009,184(1):5-12.
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