miR-200a Attenuated Doxorubicin-Induced Cardiotoxicity through Upregulation of Nrf2 in Mice.
MouseChemical/toxinC57BL/6JMalen = Echocardiography in six mice per group; n = 10 per group fo…Tail vein injection for AAV9 delivery; intramyocardial injection into the left ventricle for the adenoviral Nrf2 shRNAPre-treatment: AAV9-miR-200a given 4 weeks before doxorubicin challenge
Model: Doxorubicin-induced cardiotoxicity; acute model using a single intraperitoneal injection of DOX-HCl at 15 mg/kg and chronic model using intraperitoneal DOX at 5 mg/kg weekly for four injections (cumulative dose 20 mg/kg)
miR-200a was decreased in doxorubicin-treated hearts. AAV9-mediated miR-200a overexpression restored cardiac miR-200a, blunted body weight loss, prevented the rise in cTnI and NT-proBNP, and preserved +dP/dt, ejection fraction and cardiac output after acute doxorubicin. It preserved the GSH/GSSG ra…
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