期刊
HUMAN & EXPERIMENTAL TOXICOLOGY
卷 35, 期 9, 页码 974-982出版社
SAGE PUBLICATIONS LTD
DOI: 10.1177/0960327115613844
关键词
Aristolochic acid (AA); nephrotoxicity; Danio rerio; proteinuria; creatinine; nephrin
类别
资金
- National Natural Science Funds of China [31400979, 81202584]
- major projects of independent innovation in Shandong Province [2014ZZCX02105]
To analyze the toxic effects of aristolochic acid (AA) on developed kidneys in zebrafish larvae, zebrafish at 3 days postfertilization were treated with various concentrations of AA for 24 h before the status of kidney injury was investigated from several points of view. It was found that 21% of the larvae treated with 10 mu moL/L.AA exhibited evident periocular edema. When the concentrations of AA were increased to 20 and 40 mu moUL, defect in the cardiovascular system characterized by slow heart beat and blood flow was seen coupled with periocular edema. Creatinine in the whole larval tissue determined by liquid chromatography-mass spectrometry/mass spectrometry exhibited dramatic increase in the treated groups in a dose dependent manner within a certain range of doses. Several evident protein bands were detected by sodium dodecyl sulfate polyacrylamide gel electrophoresis in supernatant of the treated larvae, indicating leakage of glomerular filtration barrier. Results of quantitative polymerase chain reaction show that the messenger RNA expression of nephrin in the 20 and 40 gmoL/L AA-treated groups decreased to 0.58 0.062 and 0.37 0.075-folds of the control, respectively. Kidney damage was further confirmed by the histological changes in paraffin sections of treated larvae, for example, cystic glomeruli and disorganized epithelia cells of pronephric tubules. Our results revealed that AA exerted toxic effects on developed kidney of zebrafish larvae in a dose dependent manner and podocyte dysfunction may be involved in the kidney injury and proteinuria.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据