Short- and long-term effects of (−)-epicatechin on myocardial ischemia-reperfusion injury

Abstract

Epidemiological studies have shown a correlation between flavonoid-rich diets and improved cardiovascular prognosis. Cocoa contains large amounts of flavonoids, in particular flavanols (mostly catechins and epicatechins). Flavonoids possess pleiotropic properties that may confer protective effects to tissues during injury. We examined the ability of epicatechin to reduce short-and long-term ischemia-reperfusion (I/R) myocardial injury. Epicatechin (1 mg.kg(-1).day(-1)) pretreatment (Tx) was administered daily via oral gavage to male rats for 2 or 10 days. Controls received water. Ischemia was induced via a 45-min coronary occlusion. Reperfusion was allowed until 48 h or 3 wk while Tx continued. We measured infarct (MI) size (%), hemodynamics, myeloperoxidase activity, tissue oxidative stress, and matrix metalloproteinase-9 (MMP-9) activity in 48-h groups. Cardiac morphometry was also evaluated in 3-wk groups. With 2 days of Tx, no reductions in MI size occurred. After 10 days, a significant approximately 50% reduction in MI size occurred. Epicatechin rats demonstrated no significant changes in hemodynamics. Tissue oxidative stress was reduced significantly in the epicatechin group vs. controls. MMP-9 activity demonstrated limited increases in the infarct region with epicatechin. By 3 wk, a significant 32% reduction in infarct size was observed with Tx, accompanied with sustained hemodynamics and preserved chamber morphometry. In conclusion, epicatechin Tx confers cardioprotection in the setting of I/R injury. The effects are independent of changes in hemodynamics, are sustained over time, and are accompanied by reduced levels of indicators of tissue injury. Results warrant the evaluation of cocoa flavanols as possible therapeutic agents to limit ischemic injury.

(−)-Epicatechin induces calcium and translocation independent eNOS activation in arterial endothelial cells

“…It is well accepted that the activation of eNOS can exert cardioprotective effects (32,18) and thus, agents that stimulate its activity may be of therapeutic interest. In support of this, we recently reported on the cardioprotective effects of EPI on animals subjected to ischemiareperfusion or permanent coronary occlusion (35,36).…”

Loss of Multidrug Resistance–Associated Protein 1 Potentiates Chronic Doxorubicin-Induced Cardiac Dysfunction in Mice

“…The protein concentrations of heart ventricle homogenates were determined with the bicinchoninic acid protein assay. The measurement of GSH and GSSG by high-performance liquid chromatography was performed exactly as described (Deng et al, 2015) and used by others (Yamazaki et al, 2008(Yamazaki et al, , 2012Yamazaki and Villarreal, 2011;Kennedy et al, 2013;Barajas-Espinosa et al, 2014). The use of authentic GSH and GSSG to develop the standard curves ensured quantitation of the correct entities by high-performance liquid chromatography, thus validating the assay.…”

Elevated Glutathione Is Not Sufficient to Protect against Doxorubicin-Induced Nuclear Damage in Heart in Multidrug Resistance–Associated Protein 1 (Mrp1/Abcc1) Null Mice

“…The HPLC assay for GSH and GSSG is based on that developed by Senft et al (2000), and is used widely (Yamazaki et al, 2008(Yamazaki et al, , 2012Yamazaki and Villarreal, 2011;Kennedy et al, 2013;Barajas-Espinosa et al, 2014). Mouse heart homogenate was diluted with 0.5 volume of buffer A containing 15% metaphosphoric acid and mixed thoroughly, followed by centrifugation at 12,000 rpm for 15 minutes at 4°C.…”