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N-乙酰半胱氨酸对大鼠戒酒及酒精诱导的不良反应的影响。

Effects of N-acetylcysteine on alcohol abstinence and alcohol-induced adverse effects in rats.

作者信息

Ferreira Seiva Fábio Rodrigues, Amauchi Juliana Fujihara, Ribeiro Rocha Katiucha Karolina, Souza Gisele Aparecida, Ebaid Geovana Xavier, Burneiko Regina Miranda, Novelli Ethel Lourenzi Barbosa

机构信息

Department of Clinical and Cardiology, School of Medicine, São Paulo State University, UNESP, 18618-000, Botucatu, São Paulo, Brazil.

出版信息

Alcohol. 2009 Mar;43(2):127-35. doi: 10.1016/j.alcohol.2008.12.003.

DOI:10.1016/j.alcohol.2008.12.003
PMID:19251114
Abstract

Alcoholism is rampant in modern society and some antioxidant compound could perhaps be useful to reduce the damage done by alcohol consumption and abstinence. The present study was undertaken to investigate the association of N-acetylcysteine (NAC) intake, alcoholism, and alcohol abstinence on lipid profile, in vivo low-density lipoprotein (LDL) oxidation, oxidative stress, and antioxidant status in serum and liver of rats. Initially, male Wistar 30 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 2 g/L NAC; (AB) changed ethanol solution to water; (AB-NAC) changed ethanol to aqueous solution 2 g/L NAC. After 15 days of the E-group division, E-E rats had higher serum alanine transaminase, lower body weight, and surface area, despite higher energy intake than C. E-E rats had also lower feed efficiency, dyslipidemia with enhanced triacylglycerol, very low-density lipoprotein (VLDL), lipid hydroperoxide (LH) and in vivo oxidized-LDL (ox-LDL). AB, E-NAC, and AB-NAC rats ameliorated serum oxidative stress markers and normalized serum lipids. E-E rats had higher hepatic LH and lower reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio than C, indicating hepatic oxidative stress. AB and E-NAC rats normalized hepatic LH, GSSG, and the GSH/GSSG ratio, compared to E-E. AB-NAC rats had the lowest serum ox-LDL, hepatic LH levels, and the highest GSH reductase activity in hepatic tissue. In conclusion, the present study brought new insights into alcohol consumption, because ethanol exposure enhanced serum in vivo ox-LDL, as well as serum and hepatic oxidative stress. N-acetylcysteine offers promising therapeutic value to inhibit ethanol-induced adverse effects. Ethanol withdrawal had beneficial effects on serum lipids, but was more effective when coupled with NAC supplementation. Ethanol abstinence and NAC intake interact synergistically, improving serum lipids and hepatic antioxidant defenses.

摘要

酗酒在现代社会中十分猖獗,一些抗氧化化合物或许有助于减轻饮酒及戒酒造成的损害。本研究旨在探讨N-乙酰半胱氨酸(NAC)摄入量、酗酒及戒酒与大鼠血清和肝脏中脂质谱、体内低密度脂蛋白(LDL)氧化、氧化应激及抗氧化状态之间的关联。最初,将30只雄性Wistar大鼠分为两组:(C组,N = 6)给予标准饲料和水;(E组,N = 24)在半自愿研究中接受标准饲料和乙醇水溶液。乙醇暴露30天后,(E)组分为四个亚组(每组N = 6):(E-E)继续饮用30%乙醇溶液;(E-NAC)饮用含2 g/L NAC的乙醇溶液;(AB)将乙醇溶液换成水;(AB-NAC)将乙醇换成2 g/L NAC的水溶液。E组划分15天后,E-E大鼠血清丙氨酸转氨酶较高,体重和表面积较低,尽管能量摄入量高于C组。E-E大鼠的饲料效率也较低,伴有血脂异常,三酰甘油、极低密度脂蛋白(VLDL)、脂质过氧化氢(LH)及体内氧化型LDL(ox-LDL)升高。AB组、E-NAC组和AB-NAC组大鼠血清氧化应激标志物改善,血脂恢复正常。E-E大鼠肝脏LH水平较高,还原型谷胱甘肽(GSH)/氧化型谷胱甘肽(GSSG)比值低于C组,表明存在肝脏氧化应激。与E-E组相比,AB组和E-NAC组大鼠肝脏LH、GSSG及GSH/GSSG比值恢复正常。AB-NAC组大鼠血清ox-LDL最低,肝脏LH水平最低,肝脏组织中谷胱甘肽还原酶活性最高。总之,本研究为饮酒带来了新的见解,因为乙醇暴露会增加血清中体内ox-LDL以及血清和肝脏的氧化应激。N-乙酰半胱氨酸在抑制乙醇诱导的不良反应方面具有潜在的治疗价值。戒酒对血脂有有益影响,但与补充NAC联合使用时更有效。戒酒和摄入NAC具有协同作用,可改善血脂和肝脏抗氧化防御。

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