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

IF 3 3区医学 Q1 OBSTETRICS & GYNECOLOGY Menopause: The Journal of The North American Menopause Society Pub Date : 2025-01-01 Epub Date: 2024-12-03 DOI:10.1097/GME.0000000000002452

Sivaporn Sivasinprasasn, Kenneth Chattipakorn, Wasana Pratchayasakul, Siriporn C Chattipakorn, Nipon Chattipakorn

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Abstract

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.

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n-乙酰半胱氨酸增强低剂量雌激素对雌激素剥夺肥胖胰岛素抵抗大鼠缺血再灌注损伤的疗效。

目的：绝经后妇女患代谢综合征和心血管疾病的风险较高，肥胖加重了这些疾病。尽管雌激素提供心脏代谢保护，但长期高剂量治疗可能有害。本研究探讨n-乙酰半胱氨酸（NAC）与低剂量雌激素联合治疗对心脏缺血再灌注（I/R）损伤雌性雌激素剥夺肥胖大鼠心脏代谢功能障碍的影响。方法：双侧卵巢切除(O)雌性Wistar大鼠饲喂高脂饲料(H) 12周。然后，给大鼠以以下方式之一治疗4周：载药(OH；香油)，常规剂量雌激素(E；50 μg/kg/d)，低剂量雌激素(e；25 μg/kg/d), NAC (N；100 mg/kg/d)，或低剂量雌二醇与NAC （eN）联合使用。各组大鼠进行心脏I/R损伤，观察左心室（LV）功能和线粒体功能（n = 6/组）。统计分析采用单因素方差分析，并进行Fisher最小显著性差异事后检验。结果：OH大鼠的体重、内脏脂肪、血浆葡萄糖和血浆胆固醇显著增加，伴有左室功能受损和心率变异性。OH-E大鼠血浆胰岛素降低，胰岛素抵抗指数稳态模型评估。OH-E和OH-eN大鼠的心率变异性和左室功能都有类似的改善。在心脏I/R期间，OH-E和OH-eN大鼠保持左心室射血分数、每搏容量和心律失常减弱。OH-E和OH-eN大鼠心肌线粒体功能受损和梗死面积也同样减少。结论：NAC联合低剂量雌激素治疗与常规剂量雌激素治疗在减轻雌激素剥夺的肥胖胰岛素抵抗大鼠心功能障碍、心肌线粒体功能障碍和保护心脏免受I/R损伤方面具有相似的疗效。

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来源期刊

Menopause: The Journal of The North American Menopause Society 医学-妇产科学

CiteScore

5.40

自引率

7.40%

发文量

330

审稿时长

3-8 weeks

期刊介绍： Menopause, published monthly, provides a forum for new research, applied basic science, and clinical guidelines on all aspects of menopause. The scope and usefulness of the journal extend beyond gynecology, encompassing many varied biomedical areas, including internal medicine, family practice, medical subspecialties such as cardiology and geriatrics, epidemiology, pathology, sociology, psychology, anthropology, and pharmacology. This forum is essential to help integrate these areas, highlight needs for future research, and enhance health care.