N-acetylcysteine with low-dose estrogen reduces cardiac ischemia-reperfusion injury

Abstract

Myocardial damage and mitochondrial dysfunction caused by cardiac ischemia-reperfusion (I/R) injury are intensified by endogenous estrogen deprivation. Although N-acetylcysteine (NAC) exerted cardioprotective effects, its benefits when used in combination with hormone therapy are unknown. We tested the hyp othesis that a combination of NAC with low-dose estrogen improves cardiometabo lic function and protects cardiac mitochondria against I/R injury, to a similar extent to regular-dose estrogen treatment, in estrogen-deprived rats. Female Wistar ra ts had a bilateral ovariectomy (OVX) or sham operation. Twelve weeks after the ope ration, OVX rats were treated with regular-dose estrogen (E; 50 μg/kg/day), low- dose estrogen (e; 25 μg/kg/day), NAC (N; 100 mg/kg/day) or combined low-dose estradiol with NAC (eN) for 4 weeks (n = 6/group). Metabolic parameters, echocardiography, heart rate variability and then cardiac I/R protocol involving 30-min coronary artery ligation, followed by 120-min reperfusion, were performed. OVX rats had increased bod y weight, visceral fat, fasting plasma glucose, HOMA-IR index, triglycerides, cholesterol and LDL levels (P < 0.05 vs sham). Only OVX-E and OVX-eN had a similarly improve d HOMA-IR index. LVEF was increased in all treatment groups, but HRV was restore d only by OVX-E and OVX-eN. After I/R, myocardial infarct size was decreased in bot h OVX-E and OVX-eN groups. OVX-E and OVX-eN rats similarly had a reduced mitochondrial ROS level and increased mitochondrial membrane potential in the ischemic myocardium. In conclusion, combined NAC with low-dose estrogen and regular-dose estrogen t herapy similarly improve cardiometabolic function, prevent cardiac mitochondrial dysfunction and reduces the infarct size in estrogen-deprived rats with cardiac I/R injury.