Comparison of Effects of Long‐Term Ethanol Consumption on the Heart and Liver of the Rat

Abstract

Alterations in heart and liver metabolism were determined periodically in Sprague-Dawley rats pair-fed a liquid diet (ethanol, 36% of calories) for times as long as 1 year. In liver mitochondria the rate of ATP synthesis was lowered significantly after ethanol administration for 1 month and longer feeding periods. In liver microsomes from ethanol-fed animals, ethanol oxidation and aniline hydroxylation increased 1.5- and 3.5-fold, respectively, after 1 month and remained elevated at the longer feeding intervals. Electron microscopic analyses of heart left ventricles revealed no alterations from ethanol consumption for 1 month. Alterations including disrupted mitochondrial cristae, dilatation of sarcoplasmic reticulum, and widening of the intercalated discs were observed after 6.5-month feeding periods. Myocardial concentrations of creatine, creatine phosphate, ATP, ADP, and Pi remained constant even after ethanol consumption for 9 months. After a 12-month feeding period slight changes in cardiac mitochondrial energy-linked properties were observed which were not as pronounced as those occurring in liver mitochondria. The activity and oligomycin sensitivity of the ATPase were not altered in cardiac mitochondria, whereas in liver preparations significant alterations in these properties of the ATPase were apparent after ethanol consumption for 1 month and the longer feeding periods. These observations suggest that the liver responds more quickly and dramatically to chronic ethanol consumption than does the heart.

Kinetics and control of oxidative phosphorylation in rat liver mitochondria after chronic ethanol feeding

“…Ethanol treatment causes tissue-specific changes in mitochondrial morphology and membrane physical properties, including effects on mitochondrial inner membrane phospholipids and alterations in the activity and kinetic properties of several mitochondrial enzymes (reviewed in [2,4]). Mitochondrially encoded subunits of electron-transport-chain complexes and ATP synthase are specifically affected, resulting in a decrease by 30-50 % in the activity of NADH dehydrogenase, cytochrome bc " complex, cytochrome oxidase and ATP synthase [1,6,24,26]. These changes in mitochondrial characteristics occur in liver over a period of 3-5 weeks of ethanol feeding by the LieberDeCarli protocol [14] and may be more extensive with other more invasive ethanol-feeding protocols.…”

The role of iNOS in alcohol-dependent hepatotoxicity and mitochondrial dysfunction in mice

“…41,42 In rats, the later stages of alcohol-dependent hepatotoxicity are associated with a decrease in the activity of the major proteins of oxidative phosphorylation. 18,43 The effects of alcohol on liver mitochondrial function in mice have not been re- Data represent mean Ϯ SEM for 6 pairs of wild-type mice on ethanol-containing diet (WT ETOH) or control diet (WT) and iNOS Ϫ/Ϫ mice on ethanol-containing diet (iNOS Ϫ/Ϫ ETOH) or control diet (iNOS Ϫ/Ϫ ).…”

Chronic Alcohol Consumption Increases the Sensitivity of Rat Liver Mitochondrial Respiration to Inhibition by Nitric Oxide

“…31,32 These include structurally deformed and swollen organelles with changes in physical properties of the membrane and a decrease in the activity of respiratory complexes that contain mitochondrially encoded polypeptides. 31,33 In this study, these data were confirmed with chronic ethanol feeding resulting in a significant decrease in oxygen consumption, in the presence of complex I, II, or IV substrates. 34 Ethanol consumption is known to increase NO levels through the enhanced activity of inducible NO synthase.…”