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摘要
We used a green fluorescent kidney line. Tg(wt1b.GFP), as a model to access the acetaminophen (AAP)induced nephrotoxicity dynamically Zebrafish (Darito rerio) embryos at different developmental stages (1260 hpf) were treated with different dosages of AAP (0-45 mM) for different time courses (12-60 h). Results showed that zebrafish embryos exhibited no evident differences in survival rates and morphological changes between the mock-treated control (0 mM) and 2 25 mM AAP-exposure (12-72 hpf) groups In contrast, after higher doses (22 5 and 45 mM) of exposure, embryos displayed malformed kidney phenotypes, such as curved, cystic pronephric tube, pronephric duct, and a cystic and atrophic glomerulus The percentages of embryos with malformed kidney phenotypes increased as the exposure dosages of AAP Increased Interestingly, under the same exposure time course (12 h) and dose (22 5 mM). embryos displayed higher percentages of severe defects at earlier developmental stage of exposure (12-24 hpf), whereas embryos displayed higher percentages of mild defects at later exposure (60-72 hpf). With an exposure time course less than 24 h of 45 mM AAP, no embryo survived by the developmental stage of 72 hpf These results indicated that MP-induced nephrotoxicity depended on the exposure dose, time course and developmental stages. Immunohistochemical experiments showed that the cells' morphologies of the pronephric tube, pronephric duct and glomerulus were disrupted by AAP, and consequently caused cell death Real-time RTPCR revealed embryos after AAP treatment decreased the expression of cox2 and bcl2, but increased p53 expression In conclusion, AAP-induc
- 出版日期2010-5
