Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: KEGG:D00031 (Glutathione)
5,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The UW solution for preservation of the liver, kidney, and pancreas contains a number of components, and the importance of each of these has not been fully resolved. In the studies reported here the importance of glutathione and adenosine is demonstrated in isolated cell models (rabbit renal tubules and rat liver hepatocytes) of hypothermic preservation and reperfusion and in dog renal transplantation. Glutathione in the UW solution is necessary for the preservation of the capability of the cell to regenerate ATP and maintain membrane integrity. Adenosine in the UW solution provides the preserved cell with substrates for the regeneration of ATP during the reperfusion period following cold storage. The omission of GHS from the UW solution results in poorer renal function in the 48 hr dog kidney preservation-transplant model. The role of other components of the UW solution is discussed including lactobionic acid; other impermeants; and the colloid, hydroxyethyl starch. It is concluded that the development of improved preservation solutions will require a more detailed understanding of the mechanism of injury due to cold storage and, once obtained, solutions more complex than the UW solution may be required for improved long-term storage of organs.
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PMID:Important components of the UW solution. 168 16

1. Rainbow trout were dosed with prochloraz by i.p. injection of sprayed food pellets. Cytochrome P-450, two P-450-dependent activities, and two conjugase activities were measured in vitro in microsomal or cytosolic fractions. 2. Prochloraz increased cytochrome P-450 in liver, intestine, and pyloric caeca: maximum response occurred at 30-100 mg/kg i.p. In cold conditions, this increase persisted for more than 8 days after injection. 3. Hepatic 7-ethoxycoumarin-O-dealkylase (ECOD) and 7-ethoxyresorufin-O-dealkylase (EROD) were inhibited by prochloraz except in one assay in warm water where they increased. In intestine and pyloric caeca, ECOD and EROD were not detected, even when cytochrome P-450 was increased. 4. UDP-glucuronosyltransferase (1-naphthol as substrate) was unchanged or inhibited after prochloraz dosing. 5. Glutathione-S-transferase (o-dinitrobenzene as substrate), was unchanged or inhibited by prochloraz. 6. The measured level of enzymic activities was the result of induction and inhibition by prochloraz residues. Variations in basal activities and perhaps in prochloraz interactions were due to temperature acclimatization.
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PMID:Effects of the fungicide prochloraz on xenobiotic metabolism in rainbow trout: in vivo induction. 275 13

The relation between adenine nucleotide liver concentrations and the viability of liver allografts after cold preservation and warm ischemia was studied. A rat model was used with storage times defined in terms of allograft viability. Livers were excised and stored for 4 hr at 4 degrees C or 1 hr at 37 degrees C (viable if transplanted) or for 8 hr at 4 degrees C or 2 hr at 37 degrees C (not viable if transplanted) in a solution containing 0.9% NaCl and 2 mM CaCl2. Adenine nucleotide, malondialdehyde, and glutathione concentrations were measured in liver biopsies at the end of the storage periods and in control livers. During cold preservation, ATP concentrations decline, but degradation is largely halted at AMP, and this is independent of the length of storage or viability of the allograft. Graft failure is not due to lack of availability of intramitochondrial substrate (AMP) for rephosphorylation to adenosine triphosphate (ATP), nor is it likely that provision of such substrate will be helpful. On the other hand, with warm ischemia, degradation to inosine, hypoxanthine and xanthine occurs and nonviable livers develop higher levels of xanthine than viable ones; in fact, xanthine concentrations provide 100% discrimination between viable and nonviable warm preserved livers. Malondialdehyde concentrations were also significantly greater in the warm preserved nonviable livers, indicating that some lipid peroxidation may occur even before reperfusion of allografts. Glutathione concentrations were similar in all experimental groups.
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PMID:Adenine nucleotide tissue concentrations and liver allograft viability after cold preservation and warm ischemia. 328 45

The purpose of this study was to determine the influence of aging on concentrations of the important aqueous-phase antioxidants in rat tissues. Ascorbic acid, glutathione and uric acid were measured in tissues and organs of male Fischer 344 rats at 6, 15 and 26 months of age. Blood, liver, lungs, heart, kidneys, brain, testes and lenses were excised rapidly and were extracted with cold metaphosphoric acid. Aging diminished the concentration of ascorbic acid in liver, lung and lens; levels in 26-month-old rats were 40-60% of those in 6-month-old rats. Glutathione content was diminished only in lens, where it decreased almost 50% between 15 and 26 months. Some age-associated increases in antioxidant levels also were seen; testis ascorbic acid and kidney glutathione levels were elevated in the old compared with the younger rats. Uric acid concentrations were much lower than glutathione or ascorbic acid concentrations in every tissue except plasma. Old rats had lower levels of uric acid in liver but higher levels in heart, kidney and testis. These results demonstrate that aqueous-phase antioxidant levels are not uniformly diminished in tissues of old rats.
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PMID:Effect of aging on aqueous-phase antioxidants in tissues of male Fischer rats. 341 12

Glutathione (GSH), together with NADPH-producing pathways and glutathione reductase, provides a defense system against oxidants. Oxidation of GSH causes stimulation of the hexose monophosphate shunt and increased production of NADPH. We have asked if hexose monophosphate shunt activity is required for the recovery of GSH following exposure of the isolated rat retina to an oxidant. Hexose monophosphate shunt activity was decreased by depleting the retina of hexose stores, before exposing the tissue to diamide (0.04-1.0mM), an oxidant for GSH, for 30 min. After exposure, retinas were transferred to either glucose-containing or glucose-free recovery medium for an additional 30 min. Control retinas kept in glucose-free, oxygenated medium (no diamide) for 90-120 min maintained GSH at 90% of the value found in retinas incubated with glucose. After exposure of hexose-depleted retinas to 0.4 mM diamide, a nearly 90% decrease in GSH was observed. When the oxidant was removed, the level of GSH returned to more than 80% of the control value in the presence or absence of glucose. In contrast, no recovery of GSH was observed after diamide treatment if the retinas were transferred to ice-cold (1-5 degrees C) media with or without glucose or if the retinas were pre-treated with 2 mM 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) to inhibit glutathione reductase. Measurements of two NADPH-producing cytosolic enzymes, namely NADP+-dependent malic enzyme and NADP+-dependent isocitrate dehydrogenase, revealed high activities. Optimum production of NADPH from malic enzyme was 0.90 nmol NADPH produced min-1 per retina, while with isocitrate dehydrogenase the average rate was 6.9 nmol NADPH produced min-1 per retina. We suggest that these enzymes together with a long-lived endogenous substrate (probably glutamate) are responsible for the recovery of GSH in hexose-depleted retinas. The present results suggest that more than one NADPH-producing system is capable of controlling the GSH concentration in retina. Studies that have focused on the hexose monophosphate shunt pathway as the sole source of NADPH for glutathione reductase in retina and other tissues may require re-evaluation depending on the overall metabolic capacity and substrate utilization of the particular tissue. Thus, the present findings are significant not only with respect to the retina but also for other tissues whose metabolic characteristics are similar to those found in the retina.
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PMID:Multiple NADPH-producing pathways control glutathione (GSH) content in retina. 380 64

Oxygen free radicals appear to be the prime cell-toxic products during cold preservation. Glutathione (GSH) seems to play a critical role in cell protection against oxidant stress. The experimental decrease of intracellular GSH in vivo may be prevented by the administration of S-adenosylmethionine (SAMe), which seems also to play an important role in preserving the structure of cell membranes. We designed our study to investigate whether the addition of SAMe to EuroCollins solution (EC) could provide a similar degree of protection as the more complex University of Wisconsin (UW) solution during cold preservation. In addition, we have investigated a possible protective action of SAMe during hepatocyte cryopreservation. Wistar rat hepatocytes (10(6) cells/ml) were stored in either EC (+/- 12 mumol/l SAMe) or UW. In parallel, hepatocytes (10(6) cells/ml) were cryopreserved in M199 culture medium (+/- SAMe) using dimethyl sulfoxide as cryoprotectant. LDH release, viability, and hepatocyte GSH and malondialdehyde (MDA) content were sequentially determined during cold preservation. There were no differences on viability or GSH and MDA content between EC+SAMe and UW stored cells, although LDH release was slightly higher in the first group. The addition of SAMe also attenuated the decrease in both viability (37 +/- 0.8 vs 53.0 +/- 7.4%, mean +/- SEM, N = 5, P < 0.05) and GSH content (13.4 +/- 15.1 vs 45.1 +/- 16.8%, mean +/- SEM, N = 5, P < 0.01), observed after thawing. Our results suggest that SAMe could be a useful additive for both cold storage and cryopreservation solutions of hepatocytes.
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PMID:Beneficial effect of S-adenosylmethionine during both cold storage and cryopreservation of isolated hepatocytes. 758 82

Hepatocyte suspensions provide a rapid method to determine how hypothermic storage affects liver cell metabolism and viability. We investigated whether reduced Glutathione (GSH) inclusion into a modified University of Wisconsin (UW) solution, has a protective effect over Glutathione derivatives, such as Glutathione-monoethylester (GSH-E), when suspensions of hepatocytes are cold stored for several days. Isolated rat liver cells were cold preserved 96 h in UW, UW plus 3 mM GSH and UW plus 3 mM GSH-E. During the cold storage, not significant changes in cell viability were observed, but the total Glutathione content was higher in systems with extracellular GSH over those with GSH-E or without. After cold storage, the liver cells were gently resuspended in Krebs-Henseleit-1% Albumin and used for 120 min of normothermic (37 degrees C) incubation. We evaluate the functional response of the cells measuring the exclusion of Trypan Blue (TBE). This response was clearly different in preserved cells in presence of GSH. These results indicate a protective role of extracellular Glutathione, due to an accumulation of it, rather than the derivative, for hepatic cell during the cold storage in UW solutions. And also, it is possible to extend experiments with hepatocytes from a single cell isolation over 4 or more consecutive days.
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PMID:Protective effect of glutathione (GSH) over glutathione monoethyl-ester (GSH-E) on cold preservation of isolated rat liver cells. 777 58

Glutathione and glyoxalase II levels were evaluated in cytosolic and mitochondrial compartments of rat liver after 7 and 24 hr of cold storage in University of Wisconsin (UW) and Euro-Collins solutions. 1-4 A similar time-dependent depletion of cytosolic glutathione up to about 60% of control values was observed in both Euro-Collins and UW solutions. Cytosolic glyoxalase II showed activity oscillations in livers stored in Euro-Collins but not in UW. Mitochondrial glutathione and glyoxalase II were severely depleted soon after 7 hr of cold storage in Euro-Collins, whereas the same parameters did not change in liver stored in UW after 24 hr. UW is confirmed to be the most suitable solution for liver cold storage and we conclude that mitochondrial glutathione and glyoxalase II can be important parameters in assessing mitochondrial and cell function.
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PMID:Glyoxalase II and glutathione levels in rat liver mitochondria during cold storage in Euro-Collins and University of Wisconsin solutions. 862 10

In rat liver and kidney preservation, hepatic and renal uptake of 3H-adenosine, 3H-glutathione, and 3H-raffinose from University of Wisconsin solution and diffusion to the interstitial space were measured. At 4 degrees C only 0.38+/-0.47% and 2+/-0.92% of the total 3H-adenosine remained in the kidney and in the liver, respectively, but at 37 degrees C the amount remaining was 1+/-1% and 12+/-3% (P<0.001). Hepatic and renal uptake of the impermeant 3H-raffinose was unaffected by temperature. During flush out, interstitial accumulation of adenosine was significantly higher in livers than in kidneys and decreased during 24-h cold storage. Glutathione accumulation in the interstitial space was two orders of magnitude lower than 3H-adenosine accumulation and comparable to the impermeant raffinose. In summary, the bioavailability of components of preservation solutions at 4 degrees C is lower than at physiological temperatures, so that the application of cytoprotectants at 37 degrees C to organ donors, rather than simple addition to the cold storage solution, might improve cold storage preservation of livers and kidneys.
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PMID:Effect of temperature on hepatic and renal uptake of components from University of Wisconsin solution. 956 5

High yields of intact parenchymal cells are produced by the two-step Digitonin-collagenase perfusion of whole liver, and it has gained wide acceptance for biochemical and cellular analyses of zonal hepatocytes. The development reached by this methodology is in contrast to the time-limited use of the isolated cells unless those other methods, such as primary cultures, are employed. An alternative option to have cells ready to be used for several days, is the cold storage in University of Wisconsin solution as a preservation solution. This procedure is easy, not too expensive, and does not require specialized equipment. We study the competence of this system to maintain liver cells: mixed or total cells and cell-enriched fractions. We affirm viability of hepatocytes during hypothermic storage (UW-96 h-4 degrees C) by Trypan Blue exclusion, the capacity to retain cytoplasmic enzymes, metabolic competence to maintain total Glutathione content, and immunocytochemistry (gene detection). After 96 h of cold storage, mixed cells and cell-enriched fractions, were submitted to normothermic incubation (120 min, 37 degrees C) and we check Trypan Blue exclusion, cytoplasmic enzyme release, and the capacity of cell populations to synthesize urea. The results show that it is possible to use, after several days of storage, mixed liver cells and cell-enriched fractions in metabolic and gene expression studies. This procedure allows us to reduce the number of experimental animals needed, to save experimental time and costs, and to facilitate further studies in vitro about the basis and consequences of metabolic heterogeneity of the liver cell plate.
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PMID:Hypothermic storage of periportal and perivenous rat hepatocytes. 971 Mar 3


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