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L M DeCarli

Publications and source records attributed to L M DeCarli.

At least 37 records · Page 2Linked to original sources
PubMed1975

Alcoholic liver injury: experimental models in rats and baboons.

A model has been developed for the administration to rats and baboons of ethanol as part of a nutritionally adequate liquid diet. With this regimen, ethanol intake was much higher than with conventional procedures. All animals gained or maintained their body weight, and liver morphology was normal in the controls. Isocaloric substitution of carbohydrate by ethanol (36% of total calories in rats and 50% in baboons) resulted in the production of fatty liver in all animals, while the baboons also developed alcoholic hepatitis and cirrhosis with increased activities of serum glutamic oxaloacetic transaminase. Inebriation and manifestation of dependence upon withdrawal of the diet were observed in baboons and quantitated in the rat. Chemical alterations produced by ethanol at the fatty liver stage were characterized by hyperlipemia, striking triglyceride accumulation in the liver and enhanced activities of microsomal drug metabolizing enzymes, including the microsomal ethanol oxidizing system (MEOS). Ultrastructural changes of the mitochondria and the endoplasmic reticulum were already present at the fatty liver stage and persisted throughout the hepatitis and cirrhosis. The lesions were similar to those observed in alcoholics (including the inflammation and the central sclerosis), and differed strikingly from the alterations produced by other models of liver injury. In showing that all aspects of liver injury observed in alcoholics can be reproduced in animals by the feeding of pure ethanol with an adequate diet, this study incriminates ethanol itself as a cause for the hepatic complications. This new experimental model is proposed as a tool for the study of the pathogenesis and treatment of alcoholic liver injury and dependence.

Alcoholism↗
PubMed1972

Effect of ethanol on cholesterol and bile acid metabolism.

Ethanol feeding increased significantly levels of hepatic esterified cholesterol and serum free and esterified cholesterol in rats. Incorporation of intraperitoneally administered [(14)C]acetate into cholesterol was significantly increased. Labeling of cholesterol was also enhanced in liver slices from animals pretreated with ethanol and incubated with [(14)C]-acetate. Ethanol consumption prolonged the half-excretion time of labeled cholic or chenodeoxycholic acids, increased slightly the pool size, and decreased daily excretion. By contrast, supplementation of the diet with cholesterol shortened the half-excretion time, did not modify pool size, and increased daily excretion. When ethanol and cholesterol feeding were combined, the effects of ethanol prevailed and there was suppression of the adaptive changes in bile acid metabolism induced by cholesterol feeding. There was also a greater accumulation of esterified cholesterol in the liver than that produced by cholesterol alone, ethanol administration alone, or the summation of both effects. Thus, cholesterol accumulation produced by ethanol feeding is associated with both enhanced cholesterogenesis and decreased bile acid excretion. Both mechanisms may play a role, but the latter is probably predominant in these studies in which cholesterol accumulation was markedly enhanced by the addition of cholesterol to the ethanol-containing diet.

Acetates↗
PubMed1970

Reduced nicotinamide-adenine dinucleotide phosphate oxidase: activity enhanced by ethanol consumption.

Prolonged consumption of ethanol enhances the activities of the hepatic microsomal ethanol oxidizing system and of reduced nicotinamide-adenine dinucleotide phosphate oxidase, but not of catalase. The oxidase-catalase system is not part of the microsomal ethanol oxidizing system since catalase inhibitors dissociate ethanol oxidation by the two pathways. Enhanced reduced nicotinamide-adenine dinucleotide phosphate oxidase activity may contribute to liver injury, possibly by favoring lipoperoxidation.

Alcohol Drinking↗
PubMed1969

Fatty liver produced by dietary deficiencies: its pathogenesis and potentiation by ethanol.

In a study of the pathogenesis of hepatic fat accumulation under experimental conditions mimicking chronic alcoholism, rats were fed a low-fat diet, deficient in amino acids and choline, containing either ethanol or isocaloric amounts of carbohydrate. Dietary deficiencies alone produced a moderately fatty liver after 24 days. The combination of ethanol and dietary deficiencies resulted in enhanced lipid accumulation, which was apparent after only 11 days. In an investigation of the origin of hepatic triglyceride fatty acids, the experiment was repeated after the adipose lipids had been marked by the feeding of oils containing characteristic fatty acids (linseed oil, containing linolenate, or coconut oil, containing laurate and myristate). In all animals, the fatty acid composition of the hepatic triglycerides differed markedly from that of adipose tissue; it had a larger percentage of endogenously synthesized fatty acids and a five times smaller percentage of the marker fatty acids. In addition, ethanol feeding resulted in a greater retention of the marker fatty acids in the adipose tissue. Thus, the deposition of hepatic triglycerides produced by the feeding of deficient diets is markedly potentiated by ethanol; the triglyceride fatty acids accumulated under these conditions appear to originate, for the most part, not from mobilization of depot fat, but from endogenous synthesis.

Adipose Tissue↗
PubMed1968

Ethanol oxidation by hepatic microsomes: adaptive increase after ethanol feeding.

Hepatic microsomes contain an ethanol-oxidizing system distinct from alcohol dehydrogenase. In vitro, it has characteristics comparable to those of microsomal drug-detoxifying enzymes and, in vivo, it is capable of adaptation to the administration of ethanol. The existence of this microsomal ethanol-oxidizing system may explain ultrastructural, pharmacological, and biochemical effects of ethanol.

Acetaldehyde↗
PubMed1968

Role of acetate in the reduction of plasma free fatty acids produced by ethanol in man.

To investigate the mechanism by which ethanol lowers plasma free fatty acids, we tested the ability of two products of alcohol metabolism, acetate and lactate, to lower free fatty acids in man. Sodium acetate was given orally to five healthy fasting volunteers and caused a significant fall in plasma free fatty acids. After amounts of ethanol and acetate that produced similar reductions in free fatty acids, plasma acetate increased 3- to 4-fold within 20 min. In each of three subjects the fall of free fatty acids observed after acetate ingestion occurred at plasma acetate levels less than or equal to those reached after ethanol. In all studies plasma glucose remained stable. Oral administration of sodium lactate to another volunteer in amounts sufficient to raise plasma lactate concentrations to a level similar to that found after ethanol administration failed to lower plasma free fatty acids. Thus acetate, a metabolite of ethanol, reduces plasma free fatty acids at plasma acetate levels comparable to those resulting from ethanol metabolism, which suggests that the lowering of plasma free fatty acids produced by ethanol is mediated, at least in part, by acetate.

Acetates↗
PubMed1967

Difference in hepatic metabolism of long- and medium-chain fatty acids: the role of fatty acid chain length in the production of the alcoholic fatty liver.

Replacement of dietary triglycerides containing long-chain fatty acids (LCFA) by triglycerides containing medium-chain fatty acids (MCFA) markedly reduced the capacity of alcohol to produce fatty liver in rats. After 24 days of ethanol and MCFA, the increase in hepatic triglycerides was only 3 times that of controls, whereas an 8-fold rise was observed after ethanol and LCFA. The triglyceride fatty acids that accumulated in the liver after feeding of ethanol with MCFA contained only a small percentage of the MCFA; their composition also differed strikingly from that of adipose lipids. To study the mechanism of the reduction in steatosis, we compared oxidation to CO(2) and incorporation into esterified lipids of (14)C-labeled chylomicrons or palmitate-(14)C (representing LCFA), and of octanoate-(14)C (as MCFA) in liver slices and isolated perfused livers, in the presence or absence of ethanol. Ethanol depressed the oxidation of all substrates to CO(2); MCFA, however, was much more oxidized and reciprocally much less esterified than LCFA, with a 100-fold difference in the ratio of esterified lipid-(14)C to (14)CO(2). Furthermore, in hepatic microsomal fractions incubated with alpha-glycerophosphate, octanoate was much less esterified than palmitate. This propensity of MCFA to oxidation rather than esterification represents a likely explanation for the reduction in alcoholic steatosis upon replacement of dietary LCFA by MCFA.

Animals↗