Department of Clinical and Cardiology, School of Medicine, São Paulo State University, Botucatu, São Paulo, Brazil.
Alcohol. 2009 Dec;43(8):649-56. doi: 10.1016/j.alcohol.2009.09.028.
Alcoholism has been associated with a wide range of pathologic conditions, including alcoholic heart disease (AHD). Because AHD may be associated with oxidative stress, antioxidant compounds, such as N-acetylcysteine (NAC) could be useful to control the damage done by alcohol (ethanol) consumption. To investigate the NAC effects on alcoholism and alcohol abstinence, initially, 30 male Wistar rats were divided into two groups: (C, N=6) given standard chow and water; (E, N=24) receiving standard chow and aqueous ethanol solution in semi-voluntary research. After 30 days of ethanol-exposure, (E) group was divided into four subgroups (N=6/group):(E-E) continued drinking 30% ethanol-solution; (E-NAC) drinking ethanol-solution containing 2g/L NAC; (AB) changed ethanol solution to water; (AB-NAC) changed ethanol to aqueous solution of 2g/L NAC. After 15 days of the E-group division, E-E rats had lower body weight and feed efficiency, as well as higher energy-expenditure resting metabolic rate (RMR)/body weight and VO(2) consumption/surface area. These calorimetric changes were reflected on the cardiac tissue. E-E rats had higher heart weight/body weight ratio and myocardial lipid hydroperoxide (LH), indicating AHD with hypertrophy and oxidative stress. Myocardial superoxide dismutase was higher, whereas glutathione-peroxidase (GSH-peroxidase) was lower in E-E rats than in C. The higher myocardial hydroxyacyl coenzyme-A dehydrogenase (OHADH), OHADH/citrate synthase (CS), and lactate dehydrogenase (LDH)/CS in E-E rats indicated higher fatty acid degradation relative to aerobic metabolism predisposing the lipotoxicity. AB rats had lower RMR/body weight than E-E, normalized myocardial oxidative stress, and energy metabolism. E-NAC and AB-NAC had lower RMR/body weight, myocardial LH, LDH/CS, and higher GSH-peroxidase than E-E and AB, respectively, demonstrating lower oxidative stress and higher myocardial carbohydrate oxidation. In conclusion, the present study brought new insights on alcohol consumption and AHD because ethanol-exposure enhanced energy-expenditure and induced a number of calorimetric changes, which were reflected in body weight and myocardial lipotoxicity. NAC preventing ethanol-induced calorimetric changes and reducing myocardial oxidative stress enhanced carbohydrate oxidation, thus optimizing myocardial energy metabolism in both alcoholic and abstinence condition.
酒精中毒与广泛的病理状况有关，包括酒精性心脏病（AHD）。由于 AHD 可能与氧化应激有关，因此抗氧化化合物，如 N-乙酰半胱氨酸（NAC），可能有助于控制酒精（乙醇）消耗造成的损害。为了研究 NAC 对酒精中毒和戒酒的影响，最初将 30 只雄性 Wistar 大鼠分为两组：（C，N=6）给予标准饲料和水；（E，N=24）给予标准饲料和半自愿研究中的水乙醇溶液。在接触乙醇 30 天后，（E）组分为四个亚组（N=6/组）：（E-E）继续饮用 30%乙醇溶液；（E-NAC）饮用含 2g/L NAC 的乙醇溶液；（AB）将乙醇溶液改为水；（AB-NAC）将乙醇溶液改为含 2g/L NAC 的水溶液。在 E 组分组后的 15 天内，E-E 组大鼠体重和饲料效率较低，静息代谢率（RMR）/体重和 VO（2）消耗/表面积的能量消耗较高。这些热量变化反映在心脏组织上。E-E 大鼠的心脏重量/体重比和心肌脂质过氧化物（LH）较高，表明 AHD 伴有肥大和氧化应激。E-E 大鼠的心肌超氧化物歧化酶较高，而谷胱甘肽过氧化物酶（GSH-过氧化物酶）较低。E-E 大鼠的心肌羟基酰基辅酶 A 脱氢酶（OHADH）、OHADH/柠檬酸合酶（CS）和乳酸脱氢酶（LDH）/CS 较高，表明与有氧代谢相比，脂肪酸降解更高，易发生脂毒性。AB 大鼠的 RMR/体重低于 E-E，心肌氧化应激和能量代谢正常化。E-NAC 和 AB-NAC 的 RMR/体重、心肌 LH、LDH/CS 和 GSH-过氧化物酶均低于 E-E 和 AB，表明氧化应激较低，心肌碳水化合物氧化较高。总之，本研究为酒精摄入和 AHD 带来了新的认识，因为乙醇暴露增强了能量消耗，并导致了一些热量变化，这些变化反映在体重和心肌脂毒性上。NAC 可预防乙醇诱导的热量变化并降低心肌氧化应激，从而增强酒精和戒酒状态下的心肌碳水化合物氧化，优化心肌能量代谢。
