No abstract

We aimed to evaluate the impact of hormone replacement, melatonin, or exercise alone or their combination on oxidative damage and functional status of heart, brain, and aorta of postmenopausal rats and to determine whether the signaling pathway is dependent on sirtuin-1 (SIRT1). Ovariectomized Sprague Dawley rats were orally given either a hormone replacement therapy (1 mg/kg/day17β estradiol; HRT) or melatonin (4 mg/kg/day) or HRT + melatonin treatments or tap water, while each group was further divided into sedentary and exercise (30 min/5 days/week) groups. After the heart rate measurements and memory tests were performed, trunk blood was collected at the end of the 10th week to determine metabolic parameters in serum samples. Tissue samples of abdominal aorta, heart and brain were taken for biochemical measurements and histopathological evaluation. Heart rates and memory performances of the postmenopausal rats were not changed significantly by none of the applications. Melatonin treatment or its co-administration with HRT upregulated the expressions of IL-10 and SIRT1, reduced the expressions of IL-6 and TNF-α and reduced DNA damage in the hearts and thoracic aortae of non-exercised rats. Co-administration of melatonin and HRT to exercised post-menopausal rats reduced inflammatory response and upregulated SIRT1 expression in the aortic and cardiac tissues. The present study suggests that melatonin treatment, either alone or in combination with exercise and/or HRT, alleviates oxidative injury and inflammation in the hearts and aortas of postmenopausal rats via the activity of SIRT1 signaling. Melatonin should be considered in alleviating cardiovascular disease risk in postmenopausal women.