Genistein Attenuates Postischemic Depressed Myocardial Function by Increasing Myofilament Ca²⁺ Sensitivity in Rat Myocardium¹

Abstract

The present study investigated whether genistein, a broad-spectrum tyrosine kinase inhibitor, could increase the myofilament Ca2+ sensitivity and partially reverse postischemic depressed myocardial function. Left ventricular papillary muscles were isolated from adult Wistar rats and loaded with the Ca2+ indicator, aequorin. The use of fluorocarbon immersion with hypoxia simulated a model of ischemia. Myofilament responsiveness to Ca2+ was evaluated from force-[Ca2+], relationship recorded during tetani in papillary muscles. Protein levels of troponin I (Tnl) were measured in postischemic papillary muscles with the Western blot technique. Isometric contraction was depressed during the period of ischemia and remained low after 60 min of reoxygenation without a corresponding significant change of peak [Ca2+], in the control group (n = 7). In contrast, the depression of isometric contraction was ameliorated during ischemia in muscle preparations in the presence of genistein (2 μM; n = 8), and postischemic depressed myocardial contractility partially recovered after a 60-min reperfusion. The myofilament Ca2+ responsiveness was significantly increased in papillary muscles in the presence of genistein. Protein levels of Tnl were reduced in postischemic papillary muscles, whereas genistein partially restored decreased protein levels of Tnl. Our results reveal that genistein produces an effective attenuation of postischemic depressed myocardial function and improves myofibrillar Ca2+ responsiveness in rat myocardium.

Retracted: Genistein improves liver function and attenuates non‐alcoholic fatty liver disease in a rat model of insulin resistance

“…34 The soy isoflavones have been reported to be responsible for the beneficial effects of soy foods against a number of diseases. [35][36][37] Genistein has also been reported to have various bioactivities, such as a radical-scavenging action, activation of antioxidant enzymes, suppression of oxidative DNA damage, reduction of methyl glyoxal-induced mononuclear cell apoptosis, prevention of LDL oxidation, 38,39 and inhibition of NT formation. 40 Recently, genistein was shown to modulate processes involved in carbohydrate and lipid metabolism.…”

“…The soy isoflavones, particularly genistein, have undergone extensive research since their discovery in 1987 34 . The soy isoflavones have been reported to be responsible for the beneficial effects of soy foods against a number of diseases 35–37 . Genistein has also been reported to have various bioactivities, such as a radical‐scavenging action, activation of antioxidant enzymes, suppression of oxidative DNA damage, reduction of methyl glyoxal‐induced mononuclear cell apoptosis, prevention of LDL oxidation, 38,39 and inhibition of NT formation 40 .…”

Cardiovascular Toxicity of Chlorpyrifos in Female Adult Rats: A Probable Protective Effect of Phytochemical Isoflavones

“…It was revealed that GS prevents cardiac hypertrophy induced by isoproterenol in rats 19 and protects against Cardiac toxicity induced by doxorubicin in mice 16 . Furthermore, GS gives an effective reduction of postischemic depressed myocardial function and recovers myofibrillar responsiveness to Ca2+ in rats 20 . In agreement, current study verified that simultaneous administration of GS to rats exposed to CF caused significant reduction in serum levels of troponin I and MDA, indicating GS cardiac protective effect.…”

Cytoprotection by Natural and Synthetic Polyphenols in the Heart: Novel Mechanisms and Perspectives

“…In isolated ventricular papillary muscle, contractile function was depressed by hypoxia followed by reoxygenation, and this depression was ameliorated by the isoflavone genistein, which was associated with an improvement of the Ca 2+ responsiveness of the myofilaments [8]. Similarly, in cultured cardiomyocytes, hypoxia reoxygenation-induced cellular damage was attenuated with green tea polyphenols, by virtue of increased cytosolic antioxidant activity and cell viability, and reduced lipid peroxidation [9,10].…”