title: Nephroprotective role of resveratrol and ursolic Acid in aristolochic Acid intoxicated zebrafish.
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.
authors.affiliation: Department of Chemistry, Tamkang University, No. 151 Ying-chuan Road, Tamsui, New Taipei City 25137, Taiwan. dingfion@gmail.com.
authors.forename: Yu-Ju
authors.initials: YJ
authors.lastname: Ding
authors.affiliation: Department of Nephrology, Chang Gung Memorial Hospital, Keelung 20491, Taiwan. fish3970@gmail.com.
authors.forename: Chiao-Yin
authors.initials: CY
authors.lastname: Sun
authors.affiliation: Department of Mathematics, Tamkang University, Tamsui, New Taipei City 25137, Taiwan. ccwen@mail.tku.edu.tw.
authors.forename: Chi-Chung
authors.initials: CC
authors.lastname: Wen
authors.affiliation: Department of Chemistry, Tamkang University, No. 151 Ying-chuan Road, Tamsui, New Taipei City 25137, Taiwan. yauhung@mail.tku.edu.tw.
authors.forename: Yau-Hung
authors.initials: YH
authors.lastname: Chen
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D034341:Aristolochic Acids; D004625:Embryo, Nonmammalian; D004912:Erythrocytes / Q000187:drug effects / Q000502:physiology; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017382:Reactive Oxygen Species / Q000378:metabolism; D051437:Renal Insufficiency / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology / Q000627:therapeutic use*; D014315:Triterpenes / Q000494:pharmacology / Q000627:therapeutic use*; D015027:Zebrafish; D000097245:Ursolic Acid
chemical_list: D000893:Anti-Inflammatory Agents; D034341:Aristolochic Acids; D020011:Protective Agents; D017382:Reactive Oxygen Species; D000077185:Resveratrol; D013267:Stilbenes; D014315:Triterpenes; D000097245:Ursolic Acid; C000228:aristolochic acid I