Abstract：
Adolescence is characterized by increased vulnerability to addiction and ethanol (EtOH) toxicity, particularly through binge drinking (BD), a favored acute EtOH-ingestion pattern among teenagers. BD, highly pro-oxidant, induces oxidative stress (OS), affecting skeletal muscle (SKM), where selenium (Se), an antioxidant element and catalytic center of selenoproteins, is stored, among other tissues. Investigating the effects of Se supplementation on SKM after BD exposure holds therapeutic promise. For this, we randomised 32 adolescent Wistar rats into 4 groups, exposed or not to intermittent i.p. BD [BD and control (C)] (3 g EtOH per kg per day), and supplemented with selenite [BDSe and CSe] (0.4 ppm). In SKM, we examined the oxidative balance, energy status (AMPK, SIRT-1), protein turnover (IRS-1, Akt1, mTOR, IGF-1, NF-κB p65, MAFbx, ULK1, pelF2α), serum myokines (myostatin, IL-6, FGF21, irisin, BDNF, IL-15, fractalkine, FSTL-1, FABP-3), and selenoproteins (GPx1, GPx4, SelM, SelP). In the pancreas, we studied the oxidative balance and SIRT-1 expression. Selenite supplementation mitigated BD-induced OS by enhancing the expression of selenoproteins, which restored oxidative balance, notably stimulating protein synthesis and normalizing the myokine profile, leading to improved SKM mass growth and metabolism, and reduced inflammation and apoptosis (caspase-3). Selenite restoration of SelP\'s receptor LRP1 expression, reduced by BD, outlines the crucial role of SKM in the SelP cycle, linking Se levels to SKM development. Furthermore, Se attenuated pancreatic OS, preserving insulin secretion. Se supplementation shows potential for alleviating SKM damage from BD, with additional beneficial endocrine effects on the pancreas, adipose tissue, liver, heart and brain that position it as a broad-spectrum treatment for adolescent alcohol consumption, preventing metabolic diseases in adulthood.
摘要：
青春期的特征是成瘾和乙醇（EtOH）毒性的脆弱性增加，特别是通过暴饮暴食（BD），青少年中偏爱的急性EtOH摄入模式。BD,高度促氧化剂，诱导氧化应激（OS），影响骨骼肌（SKM），其中硒（Se），硒蛋白的抗氧化元件和催化中心，被存储，在其他组织中。研究补充硒对BD暴露后SKM的影响具有治疗前景。为此，我们将32只青少年Wistar大鼠随机分为4组，暴露于或不暴露于间歇性i.p.BD[BD和对照（C）]（每天每公斤3克EtOH），并补充有亚硒酸盐[BDSe和CSe](0.4ppm)。在SKM中,我们检查了氧化平衡，能量状态(AMPK，SIRT-1),蛋白质周转(IRS-1，Akt1，mTOR，IGF-1,NF-κBp65,MAFbx,ULK1,pelF2α),血清肌力因子(肌肉生长抑制素，IL-6,FGF21,irisin,BDNF,IL-15Fractalkine,FSTL-1,FABP-3),和硒蛋白(GPx1，GPx4，SelM，SelP)。在胰腺里,我们研究了氧化平衡和SIRT-1表达。亚硒酸盐补充通过增强硒蛋白的表达减轻BD诱导的OS，恢复了氧化平衡，特别是刺激蛋白质合成和正常化的肌细胞，导致改善SKM质量生长和新陈代谢，和减少炎症和细胞凋亡（caspase-3）。SelP受体LRP1表达的亚硒酸盐恢复，减少BD，概述了SKM在SelP循环中的关键作用，将硒水平与SKM发育联系起来。此外，硒减毒胰腺OS，保持胰岛素分泌。硒补充显示出减轻BD对SKM的损害的潜力，对胰腺有额外的有益内分泌作用，脂肪组织,肝脏,心脏和大脑将其定位为青少年饮酒的广谱治疗，预防成年后的代谢性疾病。
