Phytoestrogenic isoflavones daidzein and genistein reduce glucose-toxicity-induced cardiac contractile dysfunction in ventricular myocytes

Epidemiological evidence suggests a reduction in the incidence of coronary heart disease, cancer and osteoporosis in populations with a high dietary intake of plant estrogen or phytoestrogen. The clinical benefit of phytoestrogens in cereals, vegetables and medicinal plants is attracting increasing attention for the general public. In the present study, we examined the effect of phytoestrogenic isoflavones daidzein and genistein on glucose toxicity-induced cardiac mechanical malfunction simulating diabetic cardiomyopathy. Adult rat ventricular myocytes were isolated and maintained for 24 hours in normal (NG, 5.5 mM) or high glucose (HG, 25.5 MM) medium in the absence or presence of isoflavones daidzein (50 muM) or genistein (20 muM). Cardiac contractile indices were evaluated using an IonOptix(R) MyoCam system including peak shortening (PS), maximal velocity of shortening/relengthening (+/- dL/dt), time-to-PS (TPS) and time-to-90% relengthening (TR90). Myocytes maintained in HG medium displayed altered mechanical function simulating in vivo diabetes including reduced PS, +/- dL/dt and prolonged TR90 associated with normal TPS compared to those from NG myocytes. Interestingly, these HG-induced mechanical dysfunctions were abolished by co-incubation of daidzein or genistein. However, daidzein but not genistein itself depressed PS in NG myocytes. Neither daidzein nor genistein affected any other mechanical parameters tested in NG myocytes. Collectively, these data suggest that the phytoestrogenic isoflavones daidzein and genistein may reduce glucose toxicity-induced cardiac mechanical dysfunction and thus possess therapeutic potential against diabetes-associated cardiac defects.