title: Evaluation of nephrotoxic effects of aristolochic acid on zebrafish (Danio rerio) larvae.
abstract: 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 µmoL/L AA exhibited evident periocular edema. When the concentrations of AA were increased to 20 and 40 µmoL/L, 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 µmoL/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.
authors.affiliation: Biology Institute of Shandong Academy of Sciences, Jinan, China.
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.affiliation: Biology Institute of Shandong Academy of Sciences, Jinan, China hliukch@sdas.org.
authors.forename: K-C
authors.initials: KC
authors.lastname: Liu
authors.affiliation: College of Food Science and Engineering, Qilu University of Technology, Jinan, People's Repbulic of China.
authors.forename: G-J
authors.initials: GJ
authors.lastname: Sun
authors.affiliation: Biology Institute of Shandong Academy of Sciences, Jinan, China.
authors.forename: L-W
authors.initials: LW
authors.lastname: Han
authors.affiliation: Biology Institute of Shandong Academy of Sciences, Jinan, China.
authors.forename: R-C
authors.initials: RC
authors.lastname: Wang
authors.affiliation: Biology Institute of Shandong Academy of Sciences, Jinan, China.
authors.forename: W-B
authors.initials: WB
authors.lastname: Peng
authors.affiliation: Biology Institute of Shandong Academy of Sciences, Jinan, China.
authors.forename: C
authors.initials: C
authors.lastname: Sun
authors.affiliation: Epidermal Stem Cell Lab, Department of Bioscience Technology, Chung Yuan Christian University, Chung-Li, Taiwan.
authors.forename: C-D
authors.initials: CD
authors.lastname: Hsiao
authors.affiliation: Biology Institute of Shandong Academy of Sciences, Jinan, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Biology Institute of Shandong Academy of Sciences, Jinan, China.
authors.forename: H-R
authors.initials: HR
authors.lastname: Hou
mesh_terms: D000818:Animals; D034341:Aristolochic Acids / Q000633:toxicity*; D003404:Creatinine / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007668:Kidney / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism / Q000473:pathology; D007814:Larva; D011507:Proteinuria / Q000139:chemically induced / Q000196:embryology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015027:Zebrafish / Q000254:growth & development* / Q000378:metabolism
chemical_list: D034341:Aristolochic Acids; C000228:aristolochic acid I; D003404:Creatinine
keywords: Aristolochic acid (AA); Danio rerio; creatinine; nephrin; nephrotoxicity; proteinuria