Department of Physiology, Faculty of Pharmacy, University of Seville, C/Professor García González 2, 41012-Seville, Spain.
Institute of Nutrition and Food Technology "José Mataix Verdú", University of Granada, Avenida del Conocimiento s/n, 18071-Armilla, Granada, Spain.
Food Funct. 2024 Jul 29;15(15):7988-8007. doi: 10.1039/d4fo01354a.
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.
青春期的特点是易患成瘾和乙醇（EtOH）毒性，尤其是通过 binge drinking（BD），这是青少年中流行的急性 EtOH 摄入模式。BD 高度促氧化，会引起氧化应激（OS），影响骨骼肌（SKM），而硒（Se）是一种抗氧化元素，也是硒蛋白的催化中心，除了其他组织外，也储存在 SKM 中。研究 Se 补充剂对 BD 暴露后 SKM 的影响具有治疗前景。为此，我们将 32 只青春期 Wistar 大鼠随机分为 4 组，分别暴露于或不暴露于间歇性腹腔注射 BD[BD 和对照（C）]（每天每公斤 3g EtOH），并补充亚硒酸钠[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-κB p65、MAFbx、ULK1、pelF2α）、血清肌因子（肌肉生长抑制素、IL-6、FGF21、鸢尾素、BDNF、IL-15、 fractalkine、FSTL-1、FABP-3）和硒蛋白（GPx1、GPx4、SelM、SelP）。在胰腺中，我们研究了氧化平衡和 SIRT-1 表达。亚硒酸钠补充剂通过增强硒蛋白的表达缓解了 BD 引起的 OS，从而恢复了氧化平衡，特别是刺激了蛋白质合成并使肌因子谱正常化，导致 SKM 质量增长和代谢改善，减少了炎症和细胞凋亡（caspase-3）。BD 降低了 SelP 受体 LRP1 的表达，而亚硒酸钠恢复了 SelP 的表达，这突出了 SKM 在 SelP 循环中的关键作用，将 Se 水平与 SKM 发育联系起来。此外，Se 减轻了胰腺的 OS，维持了胰岛素分泌。Se 补充剂可能有助于缓解 BD 对 SKM 的损害，同时对胰腺、脂肪组织、肝脏、心脏和大脑产生有益的内分泌影响，使其成为青少年饮酒的广谱治疗方法，预防成年期代谢疾病。
