Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Conditions leading to the accumulation of unconjugated phenols and catechols were investigated in mouse livers. The formation of unconjugated hydroxylated products of added p-nitrophenol and aniline was investigated in isolated hepatocytes prepared from 48 hr fasted or fed mice or from fed mice after acetone pretreatment. 4-Nitrocatechol and p-aminophenol--the hydroxylated products of p-nitrophenol and aniline--were accumulated in cells prepared from fasting animals, while in cells prepared from fed mice these unconjugated derivatives were not detectable. The accumulation of 4-nitrocatechol and p-aminophenol was also shown in isolated hepatocytes prepared from acetone pretreated fed mice. Inhibition of glucuronidation by N6,O2-dibutyryl cAMP or by D-galactosamine increased the accumulation of 4-nitrocatechol upon addition of p-nitrophenol in cells prepared from fasted mice. Both 48 hr starvation and acetone pretreatment enhanced the activity of microsomal p-nitrophenol and aniline hydroxylase by 300% and 600%, respectively, whereas p-nitrophenol conjugation in isolated hepatocytes as well as in hepatocyte homogenates was decreased by about 80% after 48 hr starvation. Acetone pretreatment did not alter the rate of p-nitrophenol conjugation measured in liver homogenates. It is suggested that a shift from conjugation toward hydroxylation in starvation gives rise to the formation of hazardous metabolites.
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PMID:Accumulation of phenols and catechols in isolated mouse hepatocytes in starvation or after pretreatment with acetone. 319 Jul 54

Hepatic lipid synthesis was measured in rats in vivo with 3H2O, and the appearance of label in triacylglycerol and its constituent fatty acid and glycerol moieties was determined. In rats treated with Triton WR1339, the amount of newly synthesized fatty acid secreted as very-low-density lipoprotein (VLDL) triacylglycerol was greater during the dark phase of the diurnal cycle than during the light phase (11.3 versus 4.8 mumol of 3H2O/3 h per g of liver respectively). However, the total mass of VLDL triacylglycerol secreted remained constant, as did the amount of label in the secreted triacylglycerol glycerol. Newly synthesized fatty acids comprised only a small proportion of the total VLDL triacylglycerol fatty acids (TGFA) at both times (dark phase, 7.7%; light phase, 2.4%). Starvation for 24 h resulted in a small increase in the secretion of VLDL triacylglycerol. However, the contribution from newly synthesized fatty acids was decreased. Similar effects were observed in streptozotocin-diabetic animals. During the light and dark phases of the cycle, similar quantities of newly synthesized TGFA entered the hepatic cytosol, and these amounts were much smaller than those secreted as VLDL triacylglycerol. The mass of cytosolic triacylglycerol showed a diurnal variation, with a greater concentration during the light phase than in the dark. In diabetes, the mass of triacylglycerol was increased in the cytosol, as was the incorporation of labelled acylglycerol glycerol. Diabetes also abolished the diurnal variation in the quantity of cytosolic triacylglycerol. In each group of animals the specific radioactivity of the microsomal triacylglycerol was similar to that of the respective newly secreted plasma VLDL. The specific radioactivity of the cytosolic triacylglycerol was only 15.8% (dark phase) or 16.8% (light phase) that of the microsomal triacylglycerol. This increased to 35.5% in the starved animals and 40.2% in the diabetic animals.
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PMID:Secretion and storage of newly synthesized hepatic triacylglycerol fatty acids in vivo in different nutritional states and in diabetes. 321 32

Thirteen patients met our criteria for severe acetaminophen hepatotoxicity over a 5-year study period. Six patients had therapeutic misadventures (not attempting suicide), and seven were attempting suicide. Five of six patients in the therapeutic misadventure group were chronic alcoholics, and three were taking other drugs reported to cause hepatic microsomal enzyme induction. In the suicide group, two of seven patients were alcoholics, and one patient was taking another inducing drug. All six patients in the therapeutic misadventure group had nausea, vomiting, or starvation, whereas two of seven patients in the suicide group had similar characteristics. Starvation could deplete the protective factor glutathione, thus augmenting hepatotoxicity. In the therapeutic misadventure group, four of six patients developed acute tubular necrosis, as compared to two of seven in the suicide group. One patient died in each group. Clinicians should be aware of these features as part of the spectrum of acetaminophen toxicity.
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PMID:Clinical features of acetaminophen toxicity. 335 89

Two major forms of hepatic microsomal cytochrome P-450 were purified from starved and acetone-treated rats. On the basis of amino acid sequence analysis, they were identified as P-450j and P-450b. Ethanol or acetone treatment of rats caused a 9-fold increase in the amount of P-450j in liver microsomes accompanied by similar increases in the rate of NADPH-dependent metabolism of carbon tetrachloride, acetone, and benzene. Immunological experiments indicated that P-450j constitutes the major catalyst of the microsomal metabolism of the latter agents and contributes by about 50% to microsomal P-450-dependent ethanol oxidation under the conditions used. The P-450j-dependent catalytic activities had a high rate of turnover. In contrast, this was not the case for the immunodetectable P-450j, indicating the occurrence of inactive forms of this protein in microsomes. Starvation or ethanol or acetone treatment caused 10-30-fold increases in the amount of both mRNA and apoprotein of P-450b,e compared to control. Run-on experiments and the concomitant increases of the P-450b,e gene products at the mRNA and protein levels indicated the appearance of mainly a transcriptional activation by acetone, ethanol, or starvation. Fasting exerted, in addition, a pronounced synergistic effect on acetone-dependent induction of P-450b,e mRNA (3-fold), apo-P-450b,e (4.3-fold), P-450j mRNA (2-fold), and apo-P-450j (2-fold). No increase of mRNA coding for P-450j, compared to control, was seen after acetone or ethanol treatment alone. The results indicate that effects of ethanol, acetone, and/or starvation on drug and xenobiotic metabolism are caused by the induction of P-450 forms belonging to at least two gene subfamilies.
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PMID:Ethanol-, fasting-, and acetone-inducible cytochromes P-450 in rat liver: regulation and characteristics of enzymes belonging to the IIB and IIE gene subfamilies. 337 38

L-Thyroxine (T4) 5'-monodeiodinase activity (MDA) of hepatocyte cell fractions of rainbow trout was evaluated by 125I- generation following incubation with [125I-3' or 125I-5']T4 at 12 degrees. Produced in approximately equal proportions, 3,5,[125I-3'] triiodo-L-thyronine and 125I- were the sole labeled products detected by gel permeation on G-25 Sephadex columns, confirming restriction of T4 deiodination in trout to removal of a single outer-ring iodine atom. T3 underwent no significant outer-ring deiodination. MDA activity, located mainly in the microsome fraction, was optimal at a pH of approximately 7.0 and was enhanced by dithiothreitol but not by reduced glutathione. Azide, thiocyanate, thiourea, and KCl exerted no significant influence on MDA, but MDA was inhibited by: 8-anilino-1-naphthalene sulfonic acid greater than N-ethyl maleimide greater than propylthiouracil greater than sodium salicylate greater than KI. Starvation for 2 weeks depressed MDA to 46% of the level of trout fed 1% of body wt once per day. This was due to a decreased Vmax of MDA. In conclusion, trout hepatic microsomal MDA is acutely and chronically susceptible to both exogenous and endogenous factors; as an enzyme responsible for extrathyroidal T3 generation, it may exert a key role in regulating peripheral thyroidal status under both natural and experimental conditions.
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PMID:Thyroxine 5'-monodeiodinase activity in hepatocytes of rainbow trout, Salmo gairdneri: distribution, effects of starvation, and exogenous inhibitors. 355 58

The present study was designed to prepare and characterize subcellular fractions from the liver of male C57B1/6 mice, with special emphasis on their suitability for use in studies of epoxide hydrolase isozymes. The effects of different washing and pelleting procedures on the mitochondrial, microsomal and cytosolic fractions were studied. It was found that 133,000 gav for 60 min (i.e. more extensive force than the usual 105,000 gav for 60 min) was necessary to obtain a membrane-free cytosolic fraction, while one wash for microsomes and two washes for mitochondria yielded reasonably pure fractions. The purity of the different fractions obtained by differential centrifugation was then determined using established enzyme markers and morphological examination with the electron microscope. Several enzymes involved in drug metabolism were also measured in these fractions. The subcellular distributions obtained here for marker enzymes closely resemble those reported for rat liver. Starvation had no significant effect on the epoxide hydrolase activities nor did the addition of mouse bile or rat liver cytosol, which might contain inhibitors. The change in epoxide hydrolase activities with time after preparation of the subcellular fractions was studied, as well as the effect of freeze-thawing. The subfractions prepared here are suitable for the further characterization of the different forms of epoxide hydrolase present in mouse liver, as well as for other studies requiring well-characterized subfractions.
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PMID:Preparation and characterization of subcellular fractions from the liver of C57B1/6 mice, with special emphasis on their suitability for use in studies of epoxide hydrolase activities. 356 8

The effect of previous fasting on the liver morphological changes and microsomal cytochrome P-450 and b5 content was studied in thioacetamide-induced (100 mg/kg) rat liver necrosis. Starvation for 48 hours immediately before thioacetamide administration aggravates the dystrophic and necrotic processes, as revealed by histology, electron microscopic investigations and serum aminotransferase activity. The liver microsomal cytochrome P-450 concentration tended to decrease after thioacetamide challenge, with fasting resulting in a more significant loss of cytochrome P-450. Cytochrome b5 content, however, was found to increase in acute liver necrosis induced by thioacetamide.
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PMID:[Effect of prior starvation on the development of acute thioacetamide-induced liver damage in rats]. 362 Jun 73

The effect of short term starvation on the disposition kinetics of chloramphenicol was determined in goats. The same dosage level (10 mg kg-1) administered intravenously produced higher serum concentrations in the animals when they were starved than when they were not starved. This could be attributed to the significantly smaller (P less than 0.05) volume of the central compartment. Starvation significantly decreased the rate of elimination of chloramphenicol while the apparent volume of distribution of the drug was not altered. A significant decrease in the body clearance, 1.36 +/- 0.95 ml (min kg)-1 in the starved condition compared with 3.78 +/- 2.19 mg (min kg)-1 in the controls, caused a corresponding increase in the half life of chloramphenicol. The decreased rate of elimination was attributed to decreased hepatic microsomal metabolism since starvation did not change the fraction of the dose excreted unchanged in the urine. The clinical significance of the altered disposition of chloramphenicol is that administration at the usual dosing rate would lead to accumulation of the drug and eventual toxicity.
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PMID:Effect of short term starvation on disposition kinetics of chloramphenicol in goats. 373 36

The separation of rat epididymal adipocytes into plasma-membrane, mitochondrial, microsomal and cytosol fractions is described. The fractions, which were characterized by marker-enzyme analysis and electron-micrographic observation, from the cells of fed and 24 h-starved animals were used to prepare acetone/diethyl ether-dried powders for the measurement of lipoprotein lipase activities. The highest specific activities and proportion of recovered lipoprotein lipase activity were found in the plasma-membrane and microsomal fractions. The two fractions from the cells of fed rats showed similar activities and enrichments of the enzyme, these activities being higher than the plasma-membrane and lower than the microsomal activities recovered from the cells of starved animals. Chicken and guinea-pig anti-(rat lipoprotein lipase) sera were prepared, and an indirect labelled-second-antibody cellular immunoassay, using 125I-labelled rabbit anti-(chicken IgG) or 125I-labelled sheep anti-(guinea-pig IgG) antibodies respectively, for the detection of cell-surface enzyme was devised and optimized. The amount of immunodetectable cell-surface lipoprotein lipase was higher for cells isolated from fed animals than for cells from 24 h-starved animals, when either anti-(lipoprotein lipase) serum was used in the assay. The amount of immunodetectable cell-surface lipoprotein lipase fell further when starvation was extended to 48 h. The lipoprotein lipase of plasma-membrane vesicles was shown to be a patent activity and to be immunodetectable in a modification of the cellular immunoassay. Although the functional significance of the adipocyte surface lipoprotein lipase is not known, the possibility of it forming a pool of enzyme en route to the capillary endothelium is advanced.
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PMID:The lipoprotein lipase of white adipose tissue. Studies on the intracellular distribution of the adipocyte-associated enzyme. 379 91

Calcium uptake activity was assayed in liver microsomal vesicles from fed and fasted rats. This activity required ATP and was stimulated by the calcium trapping agent oxalate. The most striking feature was the low rate of calcium accumulation in liver microsomes from fasted rats. Maximal rate was inhibited up to 66 and 82% after 1 and 3 days starvation, respectively. This defective microsomal calcium handling suggests its possible involvement in the massive glycogen breakdown during starvation.
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PMID:Impaired calcium sequestration activity in liver microsomes from fasted rats. 380 85


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