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Biomedical subjects

C S Lieber

Publications and source records attributed to C S Lieber.

At least 361 records · Page 20Linked to original sources
PubMed1981

Direct measurement of neutral collagenase activity in homogenates from baboon and human liver.

Neutral collagenase (EC 3.4.24.7) has been detected in human liver biopsies, baboon liver for the first time. The reaction mixtures were composed of collagen in solution and total liver homogenate in 0.5 M Tris-HCl, pH 7.5 at 25 degree C/0.2 M NaCl/10 mM CaCl2/3 mM p-chloromercuribenzoic acid. Collagenase activity was found by directly subjecting the reaction mixtures to viscometric assay and the activity was confirmed to be due to neutral collagenase by identifying the products using disc gel electrophoresis. It proved necessary to use p-chloromercuribenzoic acid in order to reveal collagenase activity in total liver homogenates from these species. The p-chloromercuribenzoic acid served to inhibit thiol proteinases and all other signs of nonspecific collagenolysis on disc gel electrophoresis, and it was able to activate latent collagenase which trypsin could not.

Animals↗
PubMed1981

Effect of intravenous ethanol on pancreatic secretion in the conscious rat.

To study whether the secretory state of the in vivo pancreas affects its response to ethanol, we administered ethanol intravenously to conscious rats in the presence and absence of exogenous secretin. In the absence of secretin when pancreatic secretion was maintained at basal levels, intravenous ethanol produced a significant stimulation of the flow rate, bicarbonate concentration, and protein concentration. This response persisted despite elimination of gastric acid production by infusion of the H2 receptor antagonist cimetidine. In contrast, intravenous ethanol inhibited the flow rate and bicarbonate concentration when pancreatic secretion was augmented by the infusion of GIH secretin. Thus, the rat pancreas responds differently to intravenous ethanol in the basal and secretin-stimulated states. These results may account for the lack of agreement regarding the pancreatic effects of systemic ethanol.

Animals↗
PubMed1981

Sex dependent effect of chronic ethanol consumption in rats on hepatic microsome mediated mutagenicity of benzo[a]pyrene.

The effect of chronic ethanol consumption by rats on hepatic microsomal metabolism of the procarcinogen benzo[a]pyrene (B[a]P) was investigated both with respect to induction of microsomal arylhydrocarbon hydroxylase (AHH) activity and activation of B[a]P to a mutagen. In female rats, chronic ethanol ingestion produced a 42% increase in AHH activity (P less than 0.01), as measured in isolated microsomes, and also resulted in a significantly enhanced capacity (P less than 0.01) of these microsomes to activate B[a]P to a mutagen detectable in the Ames bacterial mutagenesis assay. Hepatic microsomes from male rats on the other hand did not exhibit any significant differences, either in AHH activity or in their capacity to activate B[a]P to a mutagen after chronic ethanol feeding.

Alcoholism↗
PubMed1981

Cholecystokinin and enkephalin levels following ethanol administration in rats.

Using radioimmunoassay, cholecystokinin and enkephalin levels were determined in the brain and gut of rats following ethanol administration. Acute or chronic administration of ethanol did not affect the cholecystokinin or enkephalin content of rat brain cortex, hypothalamus, striatum or proximal small bowel. This contrasts with the reports of altered levels of several classical neurotransmitters following ethanol administration.

Animals↗
PubMed1981

Effects of chronic alcohol feeding on thiamin status: biochemical and neurological correlates.

The effects of chronic alcohol feeding on thiamin status are controversial; both adverse and beneficial effects have been reported. In order to study these effects, rats and baboons were pair-fed liquid diets containing thiamin in excess of dietary requirements and either ethanol (rats 36%, baboons 50% of total calories) or the identical diet with ethanol substituted isocalorically by carbohydrate. In the rat, chronic alcohol feeding for up to 6 months had no effects on tissue thiamin measured by transketolase assay, thiamin pyrophosphate effect, or bioassay with Ochromonas danica. Shuttle box avoidance learning in rats was impaired in animals rendered thiamin deficient but not in animals fed control or alcohol-containing liquid diets. In baboons, chronic alcohol feeding for up to 3 yr had no effects on blood levels of thiamin or on urinary excretion of thiamin. Thus, chronic alcohol feeding along with nutritionally supplemented diets does not appear to significantly affect thiamin status.

Animals↗
PubMed1981

Hepatic vitamin A depletion after chronic ethanol consumption in baboons and rats.

To evaluate possible effects of alcohol consumption on vitamin A and retinol-binding protein (RBP) status, baboons were pair-fed a nutritionally adequate liquid diet containing 50% of total calories either as ethanol or isocaloric carbohydrate. Fatty liver developed after 4 months of ethanol feeding with a 59% decrease (P less than 0.001) in hepatic vitamin A levels, and fibrosis or cirrhosis developed after 24-84 months with a 95% decrease (P less than 0.001). Similarly, hepatic vitamin A levels of rats fed ethanol (36% of total calories) were decreased after 3 weeks (42%, P less than 0.01) and continued to decrease up to 9 weeks. In contrast, vitamin A contents in the kidney and testis were increase 2-3 fold in ethanol-fed rats after 9 weeks. Serum vitamin A and RBP levels were not significantly changed in rats. When dietary vitamin A was increased 5-fold, hepatic vitamin A was again decreased in ethanol-fed rats. When dietary vitamin A was virtually eliminated, the depletion rate of vitamin A from endogenous hepatic storage was 2.5 times faster in ethanol-fed rats than in controls. It is concluded that chronic ethanol consumption decreases hepatic vitamin A, and that some mechanisms other than malnutrition and malabsorption may be involved in this process.

Alcoholism↗
PubMed1981

Enhanced pulmonary and intestinal activation of procarcinogens and mutagens after chronic ethanol consumption in the rat.

Recent epidemiological surveys have indicated that alcoholics exhibit increased incidences of a variety of cancers. We have investigated, as a possible contributing factor to carcinogenesis in this population, the effect of chronic ethanol consumption on metabolic activation of procarcinogens by microsomes isolated from lungs and small intestine. These tissues are major sites through which procarcinogens enter the body and are also potential sites of procarcinogen metabolism. Rat litter-mates were pair-fed nutritionally adequate liquid diets which contained either ethanol as 36% of total energy or an equivalent energy content of carbohydrates in place of ethanol. Chronic ethanol consumption produced significant increases in pulmonary microsomal cytochrome P-450 and microsomal ethanol oxidation. The ethanol diet also enhanced the capacity of pulmonary microsomes to activate compounds present in tobacco pyrolyzates to mutagens detectable in the Ames Salmonella auxotroph reversion assay. The ethanol diet did not alter the capacity of pulmonary microsomes to hydroxylate benzo(a)pyrene (BaP) or to activate BaP to a mutagen. In contrast, microsomes from the upper small intestine of ethanol-fed rats did exhibit both higher levels of BaP hydroxylase activity and enhanced activation of BaP to a mutagen. The ethanol feeding also enhanced the capacity of the intestinal microsomes to activate to mutagens both tryptophan pyrolyzate and 2-aminofluorene but did not influence the metabolic activation of these promutagens by pulmonary microsomes. Chronic ethanol consumption thus influences carcinogen metabolism in the intestine and lung in a manner which varies with respect to both carcinogen and tissue.

Alcoholism↗
PubMed1981

Cytotoxicity of mononuclear cells and vulnerability of hepatocytes in alcoholic fatty liver of baboons.

Mononuclear cell cytotoxicity against autologous, allogeneic and xenogeneic (rabbit) hepatocytes was investigated in nine baboons fed alcohol for 17-21 months and in nine pair-fed controls. All alcohol-fed animals developed fatty liver. Cytotoxicity of mononuclear cells was not observed when rabbit hepatocytes were used as target cells, but mononuclear cells of alcohol-fed baboons were cytotoxic against hepatocytes of both control animals and hepatocytes from alcohol-fed baboons, including the animals' own hepatocytes. Increased vulnerability of hepatocytes of alcohol-fed baboons was also demonstrated since mononuclear cells of both controls and alcohol-fed animals were more cytotoxic against hepatocytes of alcohol-fed baboons than against those of controls. Thus, autologous and heterologous hepatocytes are more sensitive in the baboon than rabbit hepatocytes in demonstrating cytotoxicity already at the stage of fatty liver. Two factors are contributory: mononuclear cells cytotoxicity and vulnerability of hepatocytes.

Animals↗
PubMed1981

Ethanol, the liver, and the gastrointestinal tract.

Ethanol is easily absorbed from the intestine and diffuses quickly throughout body water. The bulk of ethanol is metabolized in the liver, where alcohol dehydrogenase, a complex mixture of isoenzymes, oxidizes ethanol to acetaldehyde. Ethanol abuse produces functional and structural changes in the gastrointestinal tract, such as in the stomach, small intestine, liver, and pancreas. Accumulating evidence suggests direct toxicity of ethanol and possibly of acetaldehyde. Fatty liver, alcoholic hepatitis, liver cirrhosis, acute and chronic gastritis, deranged structure and function of the small intestine, acute and chronic pancreatitis, and pancreatic lithiasis are some of the sequelae of ethanol abuse. Recent investigations have enhanced our understanding of the functional and structural changes of the gastrointestinal tract produced by the abuse of ethanol.

Alcoholism↗