Micronized flavonoid fraction Daflon 500 protects heart against ischemia–reperfusion injury: an old medicine for a new target

Abstract

The effects of flavonoids, in the medical formulation Daflon 500 mg (DAF) in protection of the heart against ischemia/reperfusion are not completely understood. Heart function data from Langendorff perfused Wistar rat hearts (n = 8/group) were digitally computed, and the infarct size was evaluated using 2,3,5-triphenyl tetrazolium chloride (TTC) staining and cardiac enzyme levels. The total oxidants (TOS) and antioxidants (TAS) levels as well as pro-and anti-inflammatory cytokines levels were estimated by TOS and TAS assay kits and enzyme-linked immunosorbent assay (ELISA), respectively. The antioxidant enzymes, superoxide dismutase (SOD) and catalase (CAT) were evaluated using RAN-DOX kits. Longtime treatment of DAF for 2 or 4 weeks normalized cardiac hemodynamics, vascular dynamics, and heart contractility. A significant reduction in the infarct size and cardiac enzyme levels (P < .05) was produced by DAF treatment. Short time infusion of DAF two hours before inducing ischemia yielded similar results. DAF treatment significantly (P < .05) decreased TOS levels in the perfusion effluent and increased SOD levels in the cardiomyocytes. In conclusion, treatment with DAF prevents the deterioration of cardiac function and ischemic injury caused by oxidative stress and inflammatory cytokines. The protective effects of DAF are possibly due to its antioxidant and anti-inflammatory properties.

Discrepancy between the Actions of Glucagon-like Peptide-1 Receptor Ligands in the Protection of the Heart against Ischemia Reperfusion Injury

“…These agonists showed a significant reduction in TNF-α, IL-1β, and IL-6 [44,45]. Lowering the TNF-α [46], IL-1β [47,48], and IL-6 [47] protein levels was proven to be essential in the protection of the heart against I/R injury and was shown to decrease apoptosis in cardiac myocytes [47,48]. The results of this study are consistent with the above findings.…”

“…Similar protective effects by decreasing ROS levels were reported previously by our laboratory [56,57]. We have also previously reported increased levels of SOD and CAT in other procedures that showed protection of the heart against I/R injury [46].…”

“…These agonists showed a significant reduction in TNF-α, IL-1β, and IL-6 [44,45]. Lowering the TNF-α [46], IL-1β [47,48], and IL-6 [47] protein levels was proven to be essential in the protection of In this study, we reported an increase in the levels of the antioxidant enzymes SOD and CAT after the treatment with Ex-4 and GLP-1 (9-36), which proves the presence of antioxidant activity in these compounds. Although ROS are essential for many beneficial physiological processes, their contribution to pathological conditions is indispensable [49], and GLP-1R was proven to be a strong antioxidant [50].…”

Effects of Apocynin, a NADPH Oxidase Inhibitor, in the Protection of the Heart from Ischemia/Reperfusion Injury

“…Measurement of SOD (cat# EC.1.15.1.1, Sigma, St Louis, MI, USA) is based on the principle of reduction of nitroblue tetrazolium (NBT) compound found in the reaction medium when superoxide radical, formed by the xanthine-xanthine oxidase system, cannot be removed by SOD enzyme; the results were expressed in terms of U/mg. One unit of SOD was expressed as the substance amount that caused 50% inhibition in the NBT reduction rate [56].…”

“…CAT (cat# EC 1.11.1.6, Sigma, St Louis, MI, USA) activity was measured as described previously [56]. The method is based on the direct measurement of the decrease in absorbance at 240 nm (ε240 nm = 43.6 M −1 cm −1 ) due to H 2 O 2 consumption by CAT.…”