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    题名: Developmental nephrotoxicity of aristolochic acid in a zebrafish model
    作者: Ding, Yu-Ju;Chen, Yau-Hung
    贡献者: 淡江大學化學學系
    关键词: Aristolochic acid;Heart;Nephrotoxicity;Transgenic;Zebrafish
    日期: 2012-05
    上传时间: 2012-05-23 12:09:18 (UTC+8)
    出版者: Maryland Heights: Academic Press
    摘要: Aristolochic acid (AA) is a component of Aristolochia plant extracts which is used as a treatment for different pathologies and their toxicological effects have not been sufficiently studied. The aim of this study was to evaluate AA-induced nephrotoxicity in zebrafish embryos. After soaking zebrafish embryos in AA, the embryos displayed malformed kidney phenotypes, such as curved, cystic pronephric tubes, pronephric ducts, and cases of atrophic glomeruli. The percentages of embryos with malformed kidney phenotypes increased as the exposure dosages of AA increased. Furthermore, AA-treated embryos exhibited significantly reduced glomerular filtration rates (GFRs) in comparison with mock-control littermates (mock-control: 100±2.24% vs. 10 ppm AA treatment for 3-5h: 71.48±18.84%~39.41±15.88%), indicating that AA treatment not only caused morphological kidney changes but also induced renal failure. In addition to kidney malformations, AA-treated zebrafish embryos also exhibited deformed hearts, swollen pericardiums, impaired blood circulation and the accumulation(s) of red blood cells. Whole-mount in situ hybridization studies using cmlc2 and wt1b as riboprobes indicated that the kidney is more sensitive than the heart to AA damage. Real-time PCR showed that AA can up-regulate the expression of proinflammatory genes like TNFα, cox2 and mpo. These results support the following conclusions: (1) AA-induced renal failure is mediated by inflammation, which causes circulation dysfunction followed by serious heart malformation; and (2) the kidney is more sensitive than the heart to AA injury.
    關聯: Toxicology and Applied Pharmacology 261(1), pp.59-65
    DOI: 10.1016/j.taap.2012.03.011
    显示于类别:[化學學系暨研究所] 期刊論文

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