BACKGROUND: Liver damage is a serious and sometimes fatal consequence of long-term alcohol intake, which progresses from early-stage fatty liver (steatosis) to later-stage steatohepatitis with inflammation and fibrosis/necrosis. However, very little is known about earlier stages of liver disruption that may occur in problem drinkers, those who drink excessively but are not dependent on alcohol.
METHODS: We examined how repeated binge-like alcohol drinking in C57BL/6 mice altered liver function, as compared with a single binge-intake session and with repeated moderate alcohol consumption. We measured a number of markers associated with early- and later-stage liver disruption, including liver steatosis, measures of liver cytochrome P4502E1 (CYP2E1) and alcohol dehydrogenase (ADH), alcohol metabolism, expression of cytokine mRNA, accumulation of 4-hydroxynonenal (4-HNE) as an indicator of oxidative stress, and alanine transaminase/aspartate transaminase as a measure of hepatocyte injury.
RESULTS: Importantly, repeated binge-like alcohol drinking increased triglyceride levels in the liver and plasma, and increased lipid droplets in the liver, indicators of steatosis. In contrast, a single binge-intake session or repeated moderate alcohol consumption did not alter triglyceride levels. In addition, alcohol exposure can increase rates of alcohol metabolism through CYP2E1 and ADH, which can potentially increase oxidative stress and liver dysfunction. Intermittent, excessive alcohol intake increased liver CYP2E1 mRNA, protein, and activity, as well as ADH mRNA and activity. Furthermore, repeated, binge-like drinking, but not a single binge or moderate drinking, increased alcohol metabolism. Finally, repeated, excessive intake transiently elevated mRNA for the proinflammatory cytokine IL-1B and 4-HNE levels, but did not alter markers of later-stage liver hepatocyte injury.
CONCLUSIONS: Together, we provide data suggesting that even relatively limited binge-like alcohol drinking can lead to disruptions in liver function, which might facilitate the transition to more severe forms of liver damage.
Worldwide, binge drinking is a major public health problem. The popularized health risks associated with binge drinking include physical injury and motor vehicle crashes; less attention has been given to the negative effects on the cardiovascular (CV) system. The primary aims of this review were to provide a summary of the adverse effects of binge drinking on the risk and development of CV disease and to review potential pathophysiologic mechanisms. Using specific inclusion criteria, an integrative review was conducted that included data from human experimental, prospective cross-sectional, and cohort epidemiological studies that examined the association between binge drinking and CV conditions such as hypertension, myocardial infarction, stroke, and arrhythmias. Studies were identified that examined the relationship between binge drinking and CV outcomes. Collectively, findings support that binge drinking is associated with a higher risk of pre-hypertension, hypertension, myocardial infarction, and stroke in middle-aged and older adults. Binge drinking may also have adverse CV effects in young adults (aged 18-30). Mechanisms remain incompletely understood; however, available evidence suggests that binge drinking may induce oxidative stress and vascular injury and be pro-atherogenic. Public health messages regarding binge drinking need to include the effects of binge drinking on the cardiovascular system. This article is protected by copyright. All rights reserved.