Carreras Sánchez, OlimpiaOjeda Murillo, María Luisa2025-07-182025-07-182025-04-04Romero Herrera, I. (2025). Binge drinking y adolescencia: Enfoque fisiológico integral entre el balance oxidativo, energético, metabólico y endocrino en ratas; efecto antioxidante del selenio. (Tesis Doctoral Inédita). Universidad de Sevilla, Sevilla.https://hdl.handle.net/11441/175428Adolescence is characterized by increased susceptibility to addiction and ethanol (EtOH) toxicity, particularly when consumed excessively and acutely, as in binge drinking (BD), a highly prevalent practice during this life stage. BD, which is highly pro-oxidant, induces oxidative stress (OS), a phenomenon recently linked to an energetic and metabolic imbalance, and to an insulin resistance (IR) process in the liver. Adolescents are particularly vulnerable to BD not only due to their physiological immaturity, but also because of the intense metabolic and endocrine changes they experience, which increase the risk of future IR-related metabolic complications. Selenium (Se) is an essential trace element that forms part of the catalytic center of selenoproteins, such as GPx enzymes and Selenoproteins P and M, which play a crucial antioxidant role. BD disrupts Se homeostasis and reduces the expression of key selenoproteins in organs such as the liver, kidneys and heart. Sodium selenite supplementation has been shown to exert a protective antioxidant, anti-inflammatory and antiapoptotic role against BD-induced OS during adolescence. Additionally, Se is fundamental for insulin signaling and, therefore, metabolism. However, the impact of BD and sodium selenite supplementation on the pancreas, the insulin producing organ, and two of its target tissues, adipose tissue (AT) and skeletal muscle (SKM), remains unclear. Moreover, SKM is the body's primary Se reservoir and the main glucose absorbing tissue, where both insulin and selenoproteins play an especially important role. Given the heightened vulnerability of adolescents to BD-induced metabolic disturbances, it is essential to investigate the oxidative, energetic, metabolic and endocrine balance in these tissues, as well as the potential protective role of sodium selenite supplementation, with a particular focus on SKM. This comprehensive physiological approach constitutes the general aim of this Doctoral Thesis. To this end, 32 adolescent Wistar rats were randomly assigned to four groups (n= 8), exposed or not to intermittent intraperitoneal BD [BD and control (C)] (3 g EtOH/kg/day) and supplemented with sodium selenite [BDSe and CSe] (0.4 ppm). The results confirmed that BD exposure induced systemic IR, evidenced by persistent hyperglycemia and hyperinsulinemia, along with a disruption of the insulin signaling pathway in white adipose tissue (WAT) and SKM, adding to the previously demonstrated hepatic IR. This effect was directly associated with BD-induced OS in the pancreas, SKM and WAT, triggering lipid and protein oxidation in these organs. In WAT, BD-induced OS reduced adipogenesis and lipogenesis while increasing lipolysis, leading to decreased adipose mass and promoting a proinflammatory serum adipokine profile. This contributed to the redirection of fatty acids to the liver, promoting steatosis. In SKM, OS reduced protein synthesis and increased proteolysis, disrupting the serum myokine balance and favoring muscle atrophy. These alterations in WAT and SKM demonstrate an energetic, metabolic and endocrine disruption caused by BD-induced OS. Additionally, for the first time, a reduction in selenoprotein expression in SKM was identified, linking Se status to muscle growth and development. Sodium selenite supplementation restored the oxidative balance altered by BD, thereby reestablishing insulin signaling and partially reversing generalized IR, normalizing the serum profile of adipokines and myokines, and restoring metabolism in the WAT, SKM and pancreas. Furthermore, it recovered WAT and SKM mass, optimizing their metabolic functions. These findings highlight the multisystemic negative impact of BD during adolescence and position Se as a promising broad spectrum metabolism modulating treatment, with protective effects against the oxidative, energetic, metabolic and endocrine imbalance induced by alcohol consumption.application/pdf268 p.spaAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/openAccess