Effects of creatine supplementation and estrogen replacement in combination with exercise training on cardiac function in ovariectomized hamsters

Abstract

Menopause in elder women is known to be related with the incidence and severity of many cardiovascular diseases. Creatine (Cr) and its phosphorylated form (PCr) also play an important role in muscle energetic. Reviews of previous data showed that Cr supplementation, estrogen (E₂) replacement, or exercise training alone demonstrated positive effects on cardiac function, but there is no systematic studies on the influence of combining for Cr supplementation and E₂ replacement (Cr+E₂) in non-exercise and exercise trainings on cardiac functions against failing hearts due to E₂ deficiency. In the present study, a hundred female Golden Syrian Hamsters were ovariectomized and divided into 2 groups of non exercise and exercise-trained animals. Each group was further separated into the control and 4 treatments of Cr depletion (Cr-, β-GPA 200 mg /kg BW.), Cr supplementation (Cr+, Cr monohydrate 200 mg/kg BW.), E₂ replacement (E₂, 17 β-estradiol 30 g/kg BW.), and Cr supplementation combined with E2 replacement (Cr+E₂, Cr monohydrate 200 mg/kg BW. plus β-estradiol 30 g/kg BW.) once daily. The 9-week wheel-running exercise was induced to the exercise-trained group after ovariectomy, and exercise metabolic rate (EMR) was measured weekly by using closed circuit calorimeter. After 9 weeks, all animals were sacrificed to determine 1) myocardial energy from the contents of Cr, PCr, total Cr (TCr), Cr transporter (CrT) protein, and CK activities, 2) cardiac function from QT-c interval, left ventricular developed pressure (LVDP), the maximum rate of pressure rise (dp/dt max) and 3) markers of oxidative stress from reduce glutathione (GSH), oxidized glutathione (GSSG), and an antioxidant enzyme, glutathione peroxidase (GPx). Blood samples were also drawn to measure serum IGF-1. The data showed that exercise training (10 min a day/ 5 day a week for 9 weeks) in estrogen-deficient animals could restore myocardial reserve against oxidative damage. In addition, Cr supplementation or E₂ replacement combined with exercise training yielded more valuable results for estrogen-deficient animals demonstrated by greater cardiac reserve function, greater accumulation of myocardial energy metabolic phosphate reservation via Cr metabolism, and higher level of serum IGF-I than Cr supplementation or E₂ replacement alone. Moreover, E₂ replacement combined with exercise training has been shown a greater improvement in antioxidant reservation than E2 treatment alone. Furthermore, Cr supplementation plus E₂ replacement together with exercise training yielded the most valuable results for estrogen-deficient animals demonstrated by a greater improvement in all parameters regulating cardiac functions. The present study demonstrates that creatine supplementation and estrogen replacement combined with exercise training provide protective effects on cardiac functions in estrogen-deficient hamsters, which provide valuable data for therapeutic uses against estrogen deficiency in menopausal women.