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PubMedDate not supplied

[Study of the toxic factor in liver extracts].

Dissolution of mitochondrial fraction of ischemic liver was carried out using various detergents, the most effective of which was sodium dodecylsulphate (SDS). Excess of SDS was removed by dialysis or by sorption on anion exchange resin. The optically homogenous solution obtained was subsequently purified by gel filtration on Sephadex G-75. The preparation contained two fractions: the molecular weight of the major fraction corresponded to that of gamma-globulin and the molecular weight of the minor fraction--to that of cytochrome C. Interrelation was observed between the toxic activity and hydrophobic components of the fraction isolated.

Animals↗
PubMed1951

[Liver extracts].

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Liver Extracts↗
PubMed1998

A fetal sheep liver extract reverses age-related increments in spontaneous and induced cytokine production by indirect environmental effects.

BALB/c, DBA/2 and C57BL/6 mice of different ages (ranging from 8 to 110 weeks of age) were used as spleen cell donors to assay cytokine production from ConA activated spleen and Peyer's Patch (PP) lymphocytes. As reported in an earlier publication, there was an age-related decline in IL-2 production in all strains, with a general increase in IL-4 and IL-10 production with age, this being particularly marked for PP cell preparations. Similar conclusions were reached from independent analysis of CD44hi and CD44lo cell populations in these groups (memory vs. naive cells, respectively). Interestingly, IL-6 production was dramatically increased (some 4-5-fold in the different strains) and significantly increased levels of IL-6 were detected in the serum of aged mice. A previously described sheep fetal liver extract was able to reverse, to varying degrees, these cytokine changes associated with aging. Interestingly, when cells from aged mice were adoptively transferred to lethally irradiated young (8 week) recipients, the cytokine production phenotype of cells harvested from recipient mice 3 weeks later was that of the aged donor, unless recipients were treated continually with extract. Treatment of the donor alone produced minimal changes in cytokine production 3 weeks following adoptive transfer. The effect of extract was reversed in treated aged mice by concomitant daily intravenous infusion of the competitive inhibitor of nitric oxide synthesis (NG-monomethyl-L-arginine (NMMA)), which also decreased the increased serum nitrate levels in mice treated with extract. Our data suggest an important role for reactive nitrogen products, themselves induced by fetal liver extract, in age-associated changes in cytokine production.

Adoptive Transfer↗
PubMed1965

REGULATION OF ASCORBIC ACID AND OF XYLULOSE SYNTHESIS IN LIVER EXTRACTS. THE EFFECT OF STARVATION IN VARIOUS ANIMALS.

1. The effect of starvation on the synthesis of ascorbic acid and of xylulose from glucuronolactone and from gulonate has been studied with liver extracts from cats, rabbits, hamsters, mice and guinea pigs. 2. The synthesis of ascorbic acid from glucuronolactone is decreased in all species except cats, and that from gulonate is decreased in hamsters and mice only. 3. The synthesis of xylulose from glucuronolactone was decreased in all species except cats and mice, whereas from gulonate it was enhanced in all the species examined.

Animals↗
PubMed1996

Glycerophosphorylethanolamine (GPEA) identified as an hepatocyte growth stimulator in liver extracts.

Extracts from weanling pig liver were found to act synergistically with growth factors such as hepatocyte growth factor and transforming growth factor-alpha to stimulate hepatocyte growth in serum-free cultures. In the absence of added growth factors, the extracts had no activity. The compound responsible for this activity was isolated by passing heat-treated liver extract through anion-exchange and heparin columns followed by gel filtration at neutral and low pH, reversed-phase HPLC, and a final gel filtration column at low pH. The activity was followed throughout the purification by its ability to increase substantially the incorporation of [3H]thymidine into primary rat hepatocytes cultured serum-free in the presence of hepatocyte growth factor. The active compound was identified by NMR and mass spectrometry as glycerophosphorylethanolamine (GPEA), a breakdown product of the phospholipid phosphatidylethanolamine. The ethanolamine portion of the molecule was critical for the observed activity, whereas the glycerol phosphate portion was not necessary. In the absence of added growth factors, neither GPEA nor ethanolamine had any stimulatory effect on the cells. These results demonstrate that hepatocytes grown in culture, and especially those grown in serum-free media, require a supplement of ethanolamine and/or GPEA. In the absence of these compounds, their response to growth stimuli is greatly reduced.

Animals↗
PubMed2006

Study of a novel indolin-2-ketone compound Z24 induced hepatotoxicity by NMR-spectroscopy-based metabonomics of rat urine, blood plasma, and liver extracts.

Antiangiogenic compound has been believed to be an ideal drug in the current cancer biological therapy, but the angiogenesis inhibitors suffer setback for unknown toxicity now. A novel synthetic indolin-s-ketone small molecular compound, 3Z-3-[((1)H-pyrrol-2-yl)-methylidene]-1-(1-piperidinylmethyl)-1,3-2H-indol-2-one (Z24) can inhibit angiogenesis in new blood vessels. The hepatotoxicity effects of Z24 oral administration (dosed at 60, 130 and 200 mg/kg) have been investigated in female Wistar rats by using metabonomic analysis of (1)H NMR spectra of urine, plasma and liver extracts, as well as by clinical chemistry analysis, liver histopathology and electron micrographs examination. The (1)H NMR spectra of the biofluids were analyzed visually and via pattern recognition by using principal component analysis. The metabonomic trajectory analysis on the time-related hepatotoxicity of Z24 was carried out based on the (1)H NMR spectra of urine samples, which were collected daily predose and postdose over an 8-day period. Urinary excretion of citrate, lactate, 2-oxo-glutarate and succinate increased following Z24 dosing. Increased plasma levels of lactate, TMAO and lipid were observed, with concomitant decrease in the level of glucose and phosphatidylcholine. Metabolic profiling on aqueous soluble extracts of liver tissues with the high dose level of Z24 showed an increase in lactate and glutamine, together with a decrease in glucose, glycogen and choline. On the other hand, studies on lipid soluble extracts of liver tissues with the high dose level of Z24 showed increased level in lipid triglycerides and decreased level in unsaturated fatty acids and phosphatidylcholine. Moreover, the most notable effect of Z24 on the metabolism was the reduction in the urinary levels of creatinine and TMAO and the increase in acetate, citrate, succinate and 2-oxo-glutamate with time dependence. The results indicate that in rats Z24 inhibits mitochondrial function through altering the energy and lipid metabolism, which results in the accumulation of free fatty acids and lactate because of the lack of aerobic respiration. These data show that the metabonomic approach represents a promising new technology for the toxicological mechanism study.

Animals↗
PubMed1996

Enhancing effect of the liver extract and flavin adenin dinucleotide mixture on anti-viral efficacy of interferon in patients with chronic hepatitis C.

A combined preparation of liver extract and flavin adenin dinucleotide (FAD) (Adelavin) has been widely used in patients with chronic liver diseases in Japan. One milliliter of this agent contains 15 microliters of phenol-soluble phase of liver nucleic acid fraction and 10 mg of FAD. To examine the advantages of using this preparation in the elimination of hepatitis C virus (HCV) from patients with chronic hepatitis (CH)-C receiving interferon (IFN), 2 ml of this preparation was intravenously (n = 9) or intramuscularly (n = 8) administered daily for 5 days before 6 million units of IFN-alpha was intramuscularly injected once. Before and 48 hours after the injection of IFN, serum ALT, 2'5'-oligoadenylate synthetase (2'5-AS) activity, and HCV RNA levels were measured. The daily administration of this preparation alone for 5 days did not significantly change serum ALT, 2'5-AS activities, and HCV RNA levels. The 2'5-AS activities were significantly increased by IFN after the intravenous injection of this preparation (p < 0.01), while an injection of IFN alone of this dose did not change its activities (n = 10). HCV RNA levels were significantly decreased by IFN only after the administration of the preparation (intramuscular, p < 0.01; intravenous, p < 0.01). The effect of intravenous injection of this preparation was also elicited in patients with HCV genotype II and with HCV more than 10(5) copies/ml. These results suggest that this preparation may enhance the 2'5-AS production by IFN as a result of the increase in mitochondrial adenosin triphosphate production and may be a potent agent to enhance the anti-viral efficacy of IFN in patients with CH-C.

Adult↗
PubMed1981

Presence of an intermediate synthase form during the conversion of glycogen synthase D into synthase I in rat liver extract.

When synthase D was converted into synthase I in a liver extract, it progressed through a synthase form with activity characteristics that could not be explained by a mixture of the original synthase D and the final product, synthase I. This form was distinguished by an affinity for UDP-glucose, in the absence of glucose 6-phosphate, which was intermediate between those of the two known forms.

Animals↗