Nephroprotective Role of Resveratrol and Ursolic Acid in Aristolochic Acid Intoxicated Zebrafish
Nephroprotective Role of Resveratrol and Ursolic Acid in Aristolochic Acid Intoxicated Zebrafish
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DOI：
10.3390/toxins7010097
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发表时间：
2015-01-01
期刊：
影响因子：
4.2
通讯作者：
Chen, Yau-Hung
中科院分区：
文献类型：
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作者：
Ding, Yu-Ju;Sun, Chiao-Yin;Chen, Yau-Hung
马兜铃酸（AA）的肾毒性是众所周知的，但关于AA诱导的毒性衰减的信息是有限的。本研究的目的是研究白藜芦醇（Resv）和熊果酸（UA）在斑马鱼模型中的肾保护作用。我们使用了两个转基因株系，Tg（wt 1b：EGFP）和Tg（gata 1：DsRed），通过记录肾脏和红细胞循环的细微变化来评估Resv和UA的肾保护作用。我们的研究结果表明，Resv和UA治疗可以减轻AA诱导的肾脏畸形，改善血液循环。肾小球滤过率测定显示，Resv和UA治疗均可恢复肾功能（模拟组为100%; AA治疗组为56.1% +/- 17.3%; Resv+AA组为80.2% +/- 11.3%; UA+AA组为83.1%联产物8.1%，n = 15）。此外，实时RT-PCR实验表明，用Resv或UA预处理抑制促炎基因的表达。总之，我们的研究结果表明，AA诱导的肾毒性可以通过Resv或UA预处理来减弱。因此，我们认为，斑马鱼代表了一个有效的模型，用于筛选AA-保护性天然化合物。
The nephrotoxicity of aristolochic acid (AA) is well known, but information regarding the attenuation of AA-induced toxicity is limited. The aim of the present study was to study the nephroprotective effects of resveratrol (Resv) and ursolic acid (UA) in a zebrafish model. We used two transgenic lines, Tg(wt1b:EGFP) and Tg(gata1:DsRed), to evaluate the nephroprotective effects of Resv and UA by recording subtle changes in the kidney and red blood cell circulation. Our results demonstrated that both Resv and UA treatment can attenuate AA-induced kidney malformations and improve blood circulation. Glomerular filtration rate assays revealed that both Resv and UA treatment can restore renal function (100% for Mock; 56.1% +/- 17.3% for AA-treated; 80.2% +/- 11.3% for Resv+AA; and 83.1% coproduct 8.1% for UA+AA, n = 15). Furthermore, real-time RT-PCR experiments showed that pre-treatment with either Resv or UA suppresses expression of pro-inflammatory genes. In conclusion, our findings reveal that AA-induced nephrotoxicities can be attenuated by pre-treatment with either Resv or UA. Therefore, we believe that zebrafish represent an efficient model for screening AA-protective natural compounds.