Evaluation of nephrotoxic effects of aristolochic acid on zebrafish (Danio rerio) larvae
| Autor: | Chenghua Sun, Wei-Bing Peng, Rongchun Wang, Chung-Der Hsiao, Guijin Sun, Yan Zhang, Han Lw, Hou Hr, Kechun Liu, Xiaolong Wang |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Embryo Nonmammalian Health Toxicology and Mutagenesis 030232 urology & nephrology Aristolochic acid Kidney Toxicology Bioinformatics Nephrotoxicity Podocyte Nephrin 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Edema medicine Animals Zebrafish Creatinine biology Reverse Transcriptase Polymerase Chain Reaction General Medicine biology.organism_classification Molecular biology Proteinuria 030104 developmental biology medicine.anatomical_structure chemistry Larva biology.protein Aristolochic Acids medicine.symptom |
| Zdroj: | Human & Experimental Toxicology. 35:974-982 |
| ISSN: | 1477-0903 0960-3271 |
| DOI: | 10.1177/0960327115613844 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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