Abstract
Aging women with postmenopause are particularly susceptible to cardiovascular diseases (CVDs), which are associated with the elevation of oxidative stress and mitochondrial dysfunction. Although hormone replacement therapy (HRT) has been reported to provide cardiometabolic protection, long-term HRT could be linked to CVD consequences. A novel organic therapy with spermidine has shown promise as cardioprotection in several CVDs. However, the effects of spermidine on left ventricular (LV) function, mitochondrial function and oxidative stress in estrogen-deprived aging rats have not been investigated.
To evaluate the effects of spermidine on LV function, mitochondrial function and oxidative stress in estrogen-deprived and D-galactose-induced aging rats
Twenty female Wistar rats were randomly assigned to the sham and the ovariectomy (OVX) along with D-galactose (150 mg/kg/day, s.c.) administration throughout the experiment for 12 weeks. OVX with D-galactose-treated rats were divided into three interventional groups: vehicle (ODV), spermidine (20 mg/kg/day, p.o., ODS), and estradiol (50 ug/kg/day, s.c., ODE) (n=5/group) for 8 weeks. The sham group received a vehicle (SVV, n=5). At the end, all rats underwent echocardiography, followed by euthanasia. The hearts were removed for measuring mitochondrial reactive oxygen species (ROS), mitochondrial membrane potential (MMP) changes (ΔΨm), and malondialdehyde (MDA) levels.
Rats with OVX-induced estrogen deprivation with D-galactose-induced aging had LV impairments indicated by decreased LV ejection fraction, reduced ratio of peak velocity blood flow from left ventricular relaxation in early diastole (E) to peak velocity flow by atrial contraction (A), and increased sympathovagal imbalance (elevated low/high frequency (LF/HF) ratio) (Fig. 1A-C). These estrogen-deprived aging rats also had an increase in cardiac tissue MDA levels, mitochondrial ROS production, and MMP depolarization (Fig. 1D-F). Both spermidine and estrogen similarly demonstrated a significant reduction in all of those detrimental effects, leading to improved LV function (Fig. 1A-F).
Author notes
Funding Acknowledgements: Type of funding sources: Public grant(s) – National budget only. Main funding source(s): The National Research Council of Thailand grants NRCT-Royal Golden Jubilee Program and The National Research Council of Thailand
