N-Acetylcysteine enhances low-dose estrogen efficacy against ischemia-reperfusion injury in estrogen-deprived obese insulin-resistant rats.

Objectives: Postmenopausal women are at higher risk of metabolic syndrome and cardiovascular disease, which are aggravated by obesity. Although estrogen provides cardiometabolic protection, chronic high-dose treatment could be harmful. This study investigated the efficacy of combined N-acetylcysteine (NAC) and low-dose estrogen treatment against cardiometabolic dysfunction in female estrogen-deprived obese rats with cardiac ischemia-reperfusion (I/R) injury.
Methods: Bilateral ovariectomized (O) female Wistar rats were fed a high-fat diet (H) for 12 weeks. Then, rats were treated for 4 weeks with one of the following: vehicle (OH; sesame oil), regular-dose estrogen (E; 50 μg/kg/d), low-dose estrogen (e; 25 μg/kg/d), NAC (N; 100 mg/kg/d), or combined low-dose estradiol with NAC (eN). All rats then underwent cardiac I/R injury, and the left ventricle (LV) function and mitochondrial function were investigated (n = 6/group). Statistical analysis was performed by one-way ANOVA followed by Fisher's least significant difference post hoc test.
Results: Body weight, visceral fat, plasma glucose, and plasma cholesterol were significantly increased with impaired LV function and heart rate variability in OH rats. OH-E rats had decreased plasma insulin and Homeostatic Model Assessment for Insulin Resistance index. Both OH-E and OH-eN rats had similarly improved heart rate variability and LV function. During cardiac I/R, OH-E and OH-eN rats had preserved left ventricular ejection fraction, stroke volume, and attenuated arrhythmias. Impaired cardiac mitochondrial function and infarct size were similarly reduced in OH-E and OH-eN rats.
Conclusions: Combined NAC and low-dose estrogen treatment shares similar efficacy as regular-dose estrogen in attenuating cardiac dysfunction, cardiac mitochondrial dysfunction, and protecting the heart against I/R injury in estrogen-deprived obese insulin-resistant rats.
Competing Interests: Financial disclosure/conflicts of interest: None reported.
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