Spermidine exerts cardiometabolic protection in estrogen-deprived rats via mitigating cardiac mitochondrial dysfunction and apoptosis.

Postmenopausal conditions are linked to elevated risks of various complications, particularly cardiovascular diseases (CVDs). While estrogen supplementation is a standard intervention, it increase adverse effects of CVDs and breast cancer prevalence in postmenopausal women. Spermidine, a naturally occurring polyamine, has recently emerged attention for its protective effects in heart pathologies. However, the cardioprotective effects of spermidine against estrogen deprivation-related cardiac dysfunctions remain unclear. We hypothesized that spermidine exerted cardiometabolic protection by mitigating mitochondrial dysfunction, mitochondrial dynamics alterations, oxidative stress, inflammation, and cardiac cell death in female rats with ovariectomy (OVX)-induced estrogen deprivation. Fifty female Wistar rats were divided into a sham group (n = 10) and a 12-week-OVX-operated group (n = 40). The OVX rats were randomly assigned to receive either vehicle treatment, spermidine (OS, 20 mg/kg/day, p.o., n = 10), or estradiol (OE, 50 mg/kg/day, s.c., n = 10) for 8 weeks. Echocardiography and heart rate variability (HRV) were assessed, followed by euthanasia for cardiac tissue collection and blood sampling. OVX rats exhibited impaired metabolic, mitochondrial, and autophagic functions, along with elevated oxidative stress, inflammation, and apoptosis, leading to LV dysfunction. Spermidine and estrogen equally ameliorated all cardiometabolic adverse effects in OVX-induced estrogen-deprived female rats, suggesting spermidine as a promising alternative therapy for preventing cardiometabolic dysfunction in postmenopausal women.