Nogales Fátima, Rua Rui M, Ojeda Maria Luisa, Murillo Maria Luisa, Carreras Olimpia
Department of Physiology, Faculty of Pharmacy, Seville University , 41012 Seville, Spain.
Chem Res Toxicol. 2014 Nov 17;27(11):1926-33. doi: 10.1021/tx5002628. Epub 2014 Nov 5.
Oxidative imbalance is one of the most important mechanisms of alcohol-induced injury. Acute alcohol exposure induces a significant amount of reactive oxygen species during its hepatic metabolism via the microsomal ethanol oxidizing system. During adolescence, the physiological development is still taking place; therefore, ethanol's effects differ in adolescents compared to that in adults. Because binge drinking is the most important model of ethanol intake used by adolescents and because little is known about its effects on the liver, we have used two routes of acute ethanol administration (oral and intraperitoneal) in adolescent rats in order to analyze the oxidative damage caused in the periphery and liver. Here, it has been demonstrated for the first time that binge drinking in adolescents causes peripheral oxidation of lipid and DNA as well as lipid and protein hepatic oxidation, which are related to lower glutathione peroxidise (GPx) activity, higher catalase (CAT) activity, and higher expression of NADPHoxidase, contributing to hepatic damage. In addition, it is shown that the intraperitoneal administration route results in increased oxidative damage, which is probably related to the resulting general stress response that causes higher DNA and protein oxidation due to higher NADPHoxidase expression and higher CAT and superoxide dismutase (SOD) activities. According to these results, it is concluded that binge drinking induces hepatic damage during adolescence, at least in part, as consequence of oxidative stress because the antioxidant response was insufficient to avoid liver oxidation. Alcohol administered intraperitoneally provoked more DNA oxidation than that from the oral alcohol exposure model.
氧化失衡是酒精诱导损伤的最重要机制之一。急性酒精暴露通过微粒体乙醇氧化系统在其肝脏代谢过程中诱导产生大量活性氧。在青春期，生理发育仍在进行；因此，乙醇对青少年的影响与成年人不同。由于暴饮是青少年摄入乙醇的最重要模式，且对其对肝脏的影响知之甚少，我们在青春期大鼠中采用了两种急性乙醇给药途径（口服和腹腔注射），以分析外周和肝脏中引起的氧化损伤。在此，首次证明青少年暴饮会导致外周脂质和DNA氧化以及肝脏脂质和蛋白质氧化，这与较低的谷胱甘肽过氧化物酶（GPx）活性、较高的过氧化氢酶（CAT）活性以及NADPH氧化酶的较高表达有关，从而导致肝脏损伤。此外，研究表明腹腔注射给药途径会导致氧化损伤增加，这可能与由此产生的全身应激反应有关，该反应由于较高的NADPH氧化酶表达以及较高的CAT和超氧化物歧化酶（SOD）活性而导致更高的DNA和蛋白质氧化。根据这些结果，可以得出结论，暴饮在青春期会诱导肝脏损伤至少部分是氧化应激的结果，因为抗氧化反应不足以避免肝脏氧化。腹腔注射酒精比口服酒精暴露模型引起更多的DNA氧化。
