Fig. 1.
Pharmacological and molecular characterizations of the AA-induced heart failure. (A) Human heart failure drugs moderately attenuate the AA-induced heart failure. Zebrafish embryos were treated with 10 μM AA with or without the selected human heart failure drugs furosemide, spironolactone, levosimendan, or warfarin at 1, 5, 20, or 80 μM. Among them, the best attenuation efficiency was seen with 20 μM of spironolactone. At 80 μM, all of them failed to attenuate the heart failure. The data presented are means±SEM of triplicate wells (n=3) and the experiments were repeated twice. (B) Spironolactone at 80 μM causes curvy body and necrotic tail (arrow) in developing embryos. (C) qPCR shows elevated expression of cTnT (∼1.8-fold, P=0.003) and ANP (∼1.4-fold, P=0.013) in AA-treated embryos than that in DMSO-treated embryos. AA, aristolochic acid; ANP, atrial natriuretic peptide; cTnT, cardiac troponin T; qPCR, quantitative polymerase chain reaction.