Division of Pulmonary, Allergy, and Critical Care Medicine, Emory University School of Medicine, Whitehead Biomedical Research Building, 615 Michael Street, Atlanta, GA 30322, USA.
Alcohol Alcohol. 2010 Nov-Dec;45(6):495-500. doi: 10.1093/alcalc/agq066. Epub 2010 Oct 8.
To assess the effectiveness of procysteine (PRO) supplementation provided during a period of abstinence (ABS) on alcohol-induced skeletal muscle atrophy and oxidant stress.
Age- and gender-matched Sprague-Dawley rats were fed the Lieber-DeCarli liquid diet containing either alcohol or an isocaloric substitution (control diet) for 12 week. Next, subgroups of alcohol-fed rats were fed the control diet for 2 week (ABS) supplemented with either PRO (0.35%, w/v) or vehicle. Plantaris morphology was assessed by hematoxylin and eosin staining. Total, reduced and oxidized glutathione (GSH) levels and total antioxidant potential were determined by commercially available assay kits. Antibody arrays were used to determine cytokine levels. Real-time polymerase chain reaction was used to determine gene expressions of two E3 ubiquitin ligases, atrogin-1 and muscle ring finger protein-1 (MuRF-1).
Plantaris muscles from alcohol-fed rats displayed extensive atrophy, as well as decreased GSH levels, a trend for decreased total antioxidant potential and elevated atrogin-1 and MuRF-1 mRNA levels. GSH levels and total antioxidant potential continued to decrease during 2 weeks of ABS from alcohol, which were normalized in abstinent rats provided PRO. Gene levels of both E3 ligases returned to baseline during ABS. In parallel, plantaris cross-sectional area increased in both groups during ABS.
PRO supplementation during ABS significantly attenuated alcohol-induced redox stress compared with untreated abstinent rats. Thus, our data may suggest that GSH restoration therapy may provide therapeutic benefits to the overall antioxidant state of skeletal muscle when prescribed in conjunction with an established detoxification program for recovering alcoholics.
评估在戒断期(ABS)补充脯氨酸(PRO)对酒精引起的骨骼肌萎缩和氧化应激的有效性。
将年龄和性别匹配的 Sprague-Dawley 大鼠用 Lieber-DeCarli 液体饮食喂养,其中含有酒精或等热量替代物(对照饮食),共 12 周。接下来,用对照饮食喂养酒精喂养的大鼠亚组 2 周(ABS),并补充 PRO(0.35%,w/v)或载体。通过苏木精和伊红染色评估比目鱼肌形态。通过市售试剂盒测定总、还原和氧化型谷胱甘肽(GSH)水平以及总抗氧化能力。使用抗体阵列测定细胞因子水平。实时聚合酶链反应用于测定两种 E3 泛素连接酶肌萎缩蛋白-1(atrogin-1)和肌肉环指蛋白-1(MuRF-1)的基因表达。
酒精喂养大鼠的比目鱼肌显示出广泛的萎缩,GSH 水平降低,总抗氧化能力呈下降趋势,肌萎缩蛋白-1 和 MuRF-1 mRNA 水平升高。酒精戒断期间的 2 周内,GSH 水平和总抗氧化能力持续下降,而 PRO 补充可使这些水平恢复正常。在 ABS 期间,两种 E3 连接酶的基因水平均恢复到基线。与此同时,两组在 ABS 期间比目鱼肌的横截面积均增加。
与未治疗的戒断大鼠相比,在 ABS 期间补充 PRO 可显著减轻酒精引起的氧化应激。因此,我们的数据可能表明,GSH 恢复治疗可能会在为恢复酗酒者制定的既定解毒方案的同时,为骨骼肌的整体抗氧化状态提供治疗益处。