The effects of low dietary levels of polyunsaturates on alcohol-induced liver disease in rhesus monkeys

Abstract

Rhesus monkeys that were maintained on a diet containing strongly influenced by the type and amount of dietary fat (for review, see Salem 14 ). For instance, research in baboons low, yet adequate, amounts of vitamins C and E and in which linoleate and linolenate represented 1.4% and 0.08% of the has shown that an alcohol-induced loss of certain liver polyunsaturated phospholipids is associated with the developtotal caloric intake, respectively, developed liver fibrosis after consuming alcohol (mean, 2.6 g kg 01 d 01 ) over a period of 3 ment of septal fibrosis and cirrhosis. 15 We postulated that a diet containing low amounts of essential fatty acids (EFAs) years. In the liver, several polyunsaturated fatty acids including 18:2n6, 20:4n6, and 22:6n3 decreased compared with might potentiate the alcohol-induced depletion of liver polyunsaturated phospholipids and lead to the development of dietary controls, and similar findings were also observed in plasma lipoproteins and erythrocytes. The amount of alcohol fibrosis. Some alcohol abusers may have an increased risk of depleting the liver of long-chain polyunsaturated fatty acids consumed correlated positively with plasma lipid peroxidation products, 4-hydroxynonenal (4-HNE) and 8-isopro-if they are not receiving an adequate dietary intake of EFAs.It was hypothesized that animals that are chronically fed stane F 2 a, and negatively with 20:4n6 and 22:6n3 levels. These findings imply that alcoholics who also have a marginal alcohol and maintained on a diet containing marginal amounts of essential fatty acids (EFAs) with lowered but intake of essential fatty acids and antioxidants in their diets may be at an increased risk of developing liver disease. (HEPA-adequate levels of antioxidants would develop liver disease.In the present study, rhesus monkeys were maintained on a TOLOGY 1997;26:1386-1392.) diet in which EFAs were supplied by olive oil and which also had somewhat reduced levels of vitamins E and C, and In alcoholics, poor nutrition is associated with an inthey were given free access to an artificially sweetened 7% creased incidence of and/or severity of liver disease and other ethanol solution. Indices of lipid peroxidation and alterations alcohol-related pathologies. 1-4 Alcohol-feeding studies in aniin the fatty acyl composition of tissues were used to monitor mals have been used to model some of the features of human the effects of prolonged alcohol consumption. liver disease. [5][6][7] For example, when alcohol-fed rodents are maintained on diets containing very high levels of polyunsat- MATERIALS AND METHODSurated fatty acids, animals develop fatty liver, inflammation, and fibrosis. 6,7 The hydroxy-aldehydes that result from the Animal Procedures. Animal procedures were performed in accordance with the NIH animal welfare guidelines, and the protocol alcohol-induced oxidation of these fatty acids are believed to was approved by the National Institute on Alcoholism and Alcohol stimulate stellate cell proliferation and collagen deposition, 8,9 Abuse Animal...

Effects of Different Quantities of Fat on Serum and Liver Lipids, Phospholipid Class Distribution and Fatty Acid Composition in Alcohol-Treated Rats

“…Such a wide variation in the results may be attributeed to differences in the type, duration and dose of alcohol, on the techniques and animal species used, diet, the lipid composition, tissues, and subcelular fraction analysed. The most consistent findings have been increases in oleic and linoleic acid and decreases in arachidonic acids together with decreases in other PUFA of n-6 and n-3 series (12,37,38). In our study, the percentages of linoleic acids were unaffected by either alcohol or a high fat diet, probably indicating an adequate intake and absorption of linoleate.…”

Inactivation of oxidized andS-nitrosylated mitochondrial proteins in alcoholic fatty liver of rats

“…48,49 Therefore, inhibition of ALDH2 may cause accumulation of toxic acetaldehyde and lipid aldehyde such as the 4-hydroxynonenal produced after exposure to alcohol and other toxic compounds. 50 Likewise, inhibition of ATP synthase leads to reduced levels of ATP, 43 which may shift cell death mechanisms to necrosis from apoptosis, which requires ATP as an energy source. Inhibition of many mitochondrial proteins involved in the electron transport chain such as NADH-ubiquinone oxidoreductase (complex I) would leak more reactive oxygen species, profoundly affecting mitochondrial dysfunction.…”

Translational Implications of the Alcohol-Metabolizing Enzymes, Including Cytochrome P450-2E1, in Alcoholic and Nonalcoholic Liver Disease

“…Suppressed ALDH2 activity can also be observed, as demonstrated in a few pathological conditions such as partially hepatotectomized rodents (Watanabe et al, 1985), I/R injury (Moon, Hood, et al, 2008), and cancer tissues Oshita et al, 2010;Park, Cho, Kim, & Paik, 2002). Following ALDH2 suppression, the serum and hepatic levels of lipid peroxides such as acetaldehyde, 4-HNE, MDA, and malondialdehyde-acetaldehyde adducts (MAA) were markedly elevated, as shown in alcohol-exposed monkeys (Pawlosky, Flynn, & Salem, 1997). These results are consistent with elevated levels of acetaldehyde in alcohol-exposed Aldh2-null mice (Isse, Matsuno, Oyama, Kitagawa, & Kawamoto, 2005;Kwon et al, 2014), UChA rats containing Aldh2 mutant genes (Quintanilla, Israel, Sapag, & Tampier, 2006;Quintanilla, Tampier, Sapag, & Israel, 2005), and rodents treated with disulfiram or cyanamide (Kato et al, 1990).…”