Abstract
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% ± 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.
Highlights
Serious damage to the kidney, a very delicate organ, increases the rate of uremic bleeding
Mock: Embryos were incubated in egg water; aristolochic acid (AA): Embryos were exposed to 3 ppm AA at 24–31 hpf; and resveratrol (Resv)+AA or ursolic acid (UA)+AA groups: Embryos were treated with Resv or UA at 12–24 hpf (1, 10 and 20 ppm) and exposed to AA at 24–31 hpf; (B) Survival rates of embryos in the prevention method
These results suggest that the attenuation of AA-induced kidney malformation by both Resv and UA treatment may be mediated by suppression of pro-inflammatory gene expression
Summary
Serious damage to the kidney, a very delicate organ, increases the rate of uremic bleeding. This leads to renal failure, a life-threatening disease. Most of the patients undergo dialysis as a long-term treatment because no specific medication has been developed [1]. Investigation of the causes of renal damage and development of new methods for preventing renal damage are needed. There are many risk factors that have been demonstrated to be highly associated with renal failure. Exposure to xenobiotics, such as antibiotics, heavy metals, aristolochic acid-containing traditional
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