Fig. 6.

Mechanistic studies of the potential heart failure drugs. (A) Zebrafish embryos were treated with 20 μM AA from 24 to 36 hpf, washed twice with egg water, and then replaced with H₂O or the drugs. Later in the development, the H₂O group showed 100% heart failure (i.e., 0% attenuation) but the lead compounds were able to attenuate the heart failure, albeit weaker, indicating that these drugs rescue the AA-induced heart failure through mechanisms other than direct binding. The data presented are means±SEM of triplicate wells (n=3), and the experiments have been repeated twice. (B) Time course experiment shows that the previously reported drug NS398 has an even wider time window than other drugs, with 50% efficacy near 48 hpf. (C) qPCR examining the COX-2 expression shows that inflammation was induced high by AA but suppressed by C25. The inflammation was not significantly suppressed by MEK-I and A11. The data presented are means±SEM of triplicate wells (n=3), and the experiments have been repeated at least twice. COX-2, cyclooxygenase-2.