Maintenance of adult rat liver slices in dynamic organ culture

1. Lipogenesis, as measured by the incorporation of (14)C-labelled glucose or acetate into fatty acids in liver slices, is high in foetal and adult rat liver but is low in the liver of the suckling rat, especially with glucose as substrate. 2. The rate of synthesis of non-saponifiable lipids from glucose is about 15 times as great in the liver of the 18-day foetus as in adult liver. Activity in the newborn is negligible. 3. Glucose incorporation into fat is strongly concentration-dependent in liver slices from the adult and 2-week-old rat, but less markedly so in liver slices from the foetus. 4. Changes in the activity of hepatic citrate-cleavage enzyme (ATP-citrate lyase) occur in parallel with the changes in the extent of fatty acid formation, supporting the participation of this enzyme in lipogenesis. However, NADP-malate dehydrogenase, a potential source of reduced nucleotide coenzyme for lipogenesis in the adult, could not be detected in foetal rat liver.

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An organ culture of postnatal rat liver slices

In Vitro ◽

10.1007/bf02618164 ◽

1983 ◽

Vol 19 (11) ◽

pp. 841-852 ◽

Cited By ~ 18

Author(s):

Adele Hart ◽

Frederick J. Mattheyse ◽

John B. Balinsky

Keyword(s):

Organ Culture ◽

Rat Liver ◽

Liver Slices

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The metabolic fate of the products of citrate cleavage. Adenosine triphosphate citrate lyase and nicotinamide–adenine dinucleotide phosphate-linked malate dehydrogenase in foetal and adult liver from ruminants and non-ruminants

Biochemical Journal ◽

10.1042/bj1080705 ◽

1968 ◽

Vol 108 (5) ◽

pp. 705-713 ◽

Cited By ~ 22

Author(s):

R. W. Hanson ◽

F. J. Ballard

Keyword(s):

Fatty Acids ◽

Malate Dehydrogenase ◽

Rat Liver ◽

Phosphoenolpyruvate Carboxykinase ◽

Nicotinamide Adenine Dinucleotide Phosphate ◽

Atp Citrate Lyase ◽

Adult Rat ◽

Liver Slices ◽

Citrate Lyase ◽

Foetal Rat

1. Foetal rat liver slices incorporate the C-3 of aspartate and C-2 of glutamate into fatty acids at rates equal to those observed with adult rat liver slices. Incorporation of either of these labelled carbon atoms into fatty acids would require a functioning citrate-cleavage pathway which consists of the enzymes ATP–citrate lyase, NAD–malate dehydrogenase and NADP–malate dehydrogenase. However, NADP–malate dehydrogenase is present in foetal rat liver at only 5% of the activity detectable in adult rat liver. 2. From these findings and the effect of cofactors on the formation of 14CO2 from [1,5−14C2]citrate in liver supernatant fractions (100000g), it is suggested that NADP–malate dehydrogenase limits the citrate-cleavage sequence. 3. Measurement of the citrate-cleavage pathway by incorporation studies with [3−14C]aspartate and [U−14C]glucose and by determining the activities of ATP–citrate lyase and NADP–malate dehydrogenase have shown that this sequence of reactions is present in the liver of the bovine foetus but not in the adult. However, C-2 of glutamate is not incorporated into fatty acids or non-saponifiable lipid by bovine liver slices. This finding as well as those presented above for the adult and foetal rat liver are interpreted on the basis of a competition between phosphoenolpyruvate carboxykinase and NAD–malate dehydrogenase for oxaloacetate produced by the cleavage of citrate in the cytosol.

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Precision-Cut Rat Liver Slices in Dynamic Organ Culture for Structure-Toxicity Studies

Journal of the American College of Toxicology ◽

10.3109/10915819009078767 ◽

1990 ◽

Vol 9 (6) ◽

pp. 621-627 ◽

Cited By ~ 5

Author(s):

Klaus Brendel ◽

Robyn L. Fisher ◽

Carlos L. Krumdieck ◽

A. Jay Gandolfi

Keyword(s):

Fatty Acids ◽

Organ Culture ◽

Chain Length ◽

Rat Liver ◽

Sprague Dawley ◽

Toxicity Studies ◽

Liver Slices ◽

Sprague Dawley Rat ◽

Branched Chain

We describe a novel in vitro mammalian liver system, which simplifies both metabolism and hepatotoxicity studies in a multitude of species. This system is based on mechanical cutting of slices with high precision and culture of such slices under dynamic organ culture conditions. This system permits study of intoxication or metabolism for many hours to days and is suitable for integrative biochemical assays as well as histological and morphological evaluation. We report the toxicity exhibited by the isomeric dichlorobenzenes, which in Sprague-Dawley rat liver slices is M>O>P. We also compared a series of bromobenzene analogs, which in Sprague-Dawley rat liver slices are toxic in the following sequence DBB > BB > BBN > BA > BBT > BT. The toxicity of medium chain length branched-chain fatty acids related to valproic acid also was evaluated in this system. Results show that toxicity increased with chain length in α-methyl fatty acids and depended on the location of the carboxyl group in branched-chain octanoic acids. These examples serve to illustrate the utility of precision-cut rat liver slices in dynamic organ culture for structure—toxicity studies.

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Regulation of tyrosine aminotransferase in foetal rat liver

Biochemical Journal ◽

10.1042/bj1860609 ◽

1980 ◽

Vol 186 (2) ◽

pp. 609-612 ◽

Cited By ~ 6

Author(s):

S M Andersson ◽

N C Räihä ◽

J J Ohisalo

Keyword(s):

Enzyme Activity ◽

Methyl Ester ◽

Cyclic Amp ◽

Organ Culture ◽

Rat Liver ◽

Tyrosine Aminotransferase ◽

Dibutyryl Cyclic Amp ◽

Adult Rat ◽

Foetal Rat

A specific tyrosine aminotransferase, separate from the aspartate aminotransferases, is present in low concentration in foetal rat liver at the 21st day of gestation. Intraperitoneal injections of tyrosine methyl ester into the foetuses in utero increase the activity 2-fold, whereas glucose injections decrease it. Tyrosine, dexamethasone and dibutyryl cyclic AMP induce the enzyme activity in organ culture to the same extent as in adult rat liver in vivo.

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