Long-term administration of fisetin was not as effective as short term in ameliorating IR injury in isolated rat heart

The current study aims to determine the comparative efficacy of fisetin in reducing myocardial ischemia–reperfusion injury (IR) in isolated rat hearts when the drug was given either oral or intraperitoneal (ip) for short-term and long-term administration. Rats treated with fisetin (20 mg/kg-oral/ip) for short (30 min prior to surgery) and long (15 days prior to surgery followed by 1-day washout) duration were subjected to myocardial IR using Langendorf perfusion system. Hemodynamics, cardiac injury, mitochondrial functional assessment, and fisetin levels were estimated. Unlike the long-term administration of fisetin, the short-term treated-rat heart exhibited significant cardioprotection, measured via hemodynamic indices (RPP in mmHg × beats/min × 10 (^ 4): IR — 4 ± 0.1, FIPS — 2.49 ± 0.18, FIPL — 1.87 ± 0.14), reduced infarct size (in % area of infarct: IR — 38 ± 5, FIPS — 17 ± 1, FOS — 14 ± 2), improved mitochondrial ETC enzyme activity (NQR activity in IFM: FIPS — 0.25 ± 0.016, FIPL — 0.20 ± 0.02), and declined oxidative stress (GSH in IFM: FIPS — 1.52 ± 0.14, FIPL — 1.25 ± 0.22). However, no significant difference in the protection was observed between the animals treated with oral or intraperitoneally administered fisetin. Single dose of fisetin administration before IR protocol was more effective than 15 days of fisetin-treated drug followed by 1-day washout, thus may not be suitable for long-term dietary supplement for post-surgical cardiac rehabilitation.