Oral or Intraperitoneal Binge Drinking and Oxidative Balance in Adolescent Rats

Abstract

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.

Binge ethanol exposure increases the Krüppel-like factor 11-monoamine oxidase (MAO) pathway in rats: Examining the use of MAO inhibitors to prevent ethanol-induced brain injury

“…Protein oxidation by ethanol has been documented, including in rodents exposed to binge ethanol (Nogales et al, 2014). Like MAO enzymatic activity, protein oxidation was strikingly elevated by binge ethanol exposure.…”

“…Moreover, neither binge ethanol nor MAOIs had any significant effect on the protein expression of SOD2 or catalase. Several studies have reported changes in expression/activity of SOD2 and catalase following ethanol exposure, while others have not (Carmiel-Haggai et al, 2003; Artun et al, 2010; Nogales et al, 2014). However, in the brain, catalase is largely responsible for the metabolism of ethanol to acetylaldehyde (Ledesma et al, 2014), which explains why we observed a group effect in binge ethanol-treated rats for increased catalase expression compared to control rats, regardless of MAOI administration.…”

Upregulated Autophagy in Sertoli Cells of Ethanol-Treated Rats Is Associated with Induction of Inducible Nitric Oxide Synthase (iNOS), Androgen Receptor Suppression and Germ Cell Apoptosis

“…Twelve-week-old adult male Wistar rats (250–300 g) were purchased from SLC Japan (Shizuoka, Japan) and given a single intraperitoneal injection of 40% ethanol (5 g/kg), which is consistent with animal models of acute (binge) ethanol administration [12,13,54,55,56,57]. A control group was also treated with phosphate buffered saline.…”

Binge Drinking During Adolescence Disrupts Se Homeostasis and Its Main Hepatic Selenoprotein Expression

“…However, little is known about adolescent BD and its relationship to hepatic oxidation during this developmental period. In this context, our research group has recently found liver oxidation, an imbalance in hepatic GSH and antioxidant enzymes activities, and an increase in liver NADPH‐oxidase expression in adolescent rats exposed to BD (Nogales et al., ).…”

“…Previous studies have demonstrated that chronic alcohol consumption partially decreased Se deposits in animals and patients (Park et al., ; Rua et al., ), affecting the expression of selenoproteins (Jotty et al., ) and their antioxidant properties (Ojeda et al., ; Rua et al., ). However, until now—and despite the evidence that BD provokes liver oxidation and affects several antioxidant enzymes’ activities (Nogales et al., )—nothing was known about body Se levels, Se distribution, or selenoprotein expression, especially in the liver, a tissue that is affected by EtOH consumption.…”