Alcohol Vapor Inhalation as a Model of Alcohol‐Induced Organ Disease

Abstract

Background Chronic intermittent ethanol vapor exposure (CIEV) has been used extensively to produce rodent models of alcohol dependence, but unlike other models of alcohol abuse, CIEV has not been assessed as a model of end-organ damage. The purpose of this study was to characterize the effects of CIEV on peripheral organ systems affected by alcohol abuse, including the liver, lungs and cardiovascular system. Methods Adult male Sprague-Dawley rats were exposed to daily CIEV for a period of 8 weeks (14HR ON/10HR OFF), producing blood alcohol levels of ~200 mg/dl. Controls were exposed to room air. After 8-weeks, echocardiography was performed to assess cardiac function. Indices of liver injury (alanine and aspartate aminotransferases (ALT and AST); cytochrome p450 2E1 (CYP2E1); alcohol dehydrogenase (ADH); Oil Red-O and triglyceride content; lipid peroxidation; inflammatory cytokine expression and macrophage infiltration), and lung inflammatory cell count, proinflammatory cytokine expression, and lipid peroxidation were measured. Results Left ventricular posterior wall thickness was significantly decreased, and systolic blood pressure was significantly elevated by CIEV compared to air controls. CIEV led to a significant increase in plasma ALT and triglycerides compared to room air controls. CIEV did not affect liver triglyceride content, lipid staining or peroxidation, but increased CYP2E1 and CCL2 protein expression, while decreasing ADH expression. CIEV significantly increased numbers of both PMNs and lymphocytes in the BALF, indicative of pulmonary inflammation. However, CIEV did not produce significant changes in lung mass, pulmonary lipid peroxidation, inflammatory cytokine expression, or edema. Conclusions These results show that CIEV produces hepatic, pulmonary and cardiovascular effects in rats similar to those found in other models of chronic alcohol administration. Alcohol vapor administration is a novel method of alcohol-induced tissue injury with high potential for widespread use in alcohol toxicology research.

Heavy Chronic Intermittent Ethanol Exposure Alters Small Noncoding RNAs in Mouse Sperm and Epididymosomes

“…Importantly, animals do not lose significant body weight (defined as >10%). In addition, the effects of ethanol vapor on lungs, heart, and liver are comparable to those associated with other chronic ethanol exposure models (Mouton et al, 2016 ).…”

PCSK9 inhibition as a novel therapeutic target for alcoholic liver disease

“…This discrepancy in hepatic PCSK9 levels could be attributed to distinct animal protocols of different duration specific for investigating different stage of ALD in 2 different species. Although blood alcohol levels in the vapored rats were maintained high, raning between 150 and 250 mg% 33 , plasma ALT and cytochrome P450 2E1 (CYP2E1, a marker for alcohol liver injury) showed a 2-fold increase in the alcohol-exposed group compared to the control group 67 . On the other hand, plasma ALT and AST were 4-fold elevated and hepatic CYP2E1 was remarkably upregulated in the group feeding chronic-plus-single-binge (binge alcohol-fed group) compared to a control group.…”

Chronic Ethanol Administration Prevents Compensatory Cardiac Hypertrophy in Pressure Overload

“…Ethanol vapor levels were set to achieve blood alcohol levels (BALs) of 150–200 mg/dl. We have previously shown that chronic ethanol administration at this BAL produced end organ damage including markers of hepatic injury and inflammation, decreases in left ventricular wall thickness, increases in systolic blood pressure, and pulmonary inflammatory cell infiltration (Mouton et al, 2016a). BALs were assessed from tail vein blood samples using an Analox GM7 analyzer (London, UK).…”

“…Alcohol is among the most commonly abused drug worldwide, and as such, chronic alcohol abuse creates an enormous economic burden on the healthcare system (Hasin et al, 2007). Chronic alcohol abuse has many health implications that affect multiple organ systems, including the heart (Mouton et al, 2016a, Piano, 2002). Alcoholic cardiomyopathy (ACM) is a term used to describe a dilated cardiomyopathy that is associated with chronic alcohol consumption (Piano, 2002).…”