Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020672 (hypothermia)
 17,327 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

One of the mechanisms thought to cause injury in preserved organs is the formation of oxygen free radicals. The cell is protected from oxidative stress by many defense mechanisms. A major defense mechanism involves glutathione and glutathione-dependent enzymes. During organ preservation by simple cold storage the loss of glutathione may sensitize the organ to free radical damage after transplantation. In this study we show that glutathione is depleted from the rabbit liver, kidney, and heart cold-stored (5 degrees C) for up to 72 h in the UW solution without glutathione. In the first 24 h kidney glutathione decreased to 84 +/- 3% of control values, liver glutathione decreased to 49 +/- 3% of control values, and heart glutathione decreased to 73 +/- 3% of control values. After 48 h of storage the kidney and liver lost an additional 30 and 20%, respectively, whereas heart glutathione changed very little. By 72 h all three organs had lost more than 50% of the glutathione found in freshly obtained tissue. To determine if glutathione added to the UW solution can effectively prevent this loss of glutathione during preservation, hepatocytes were cold-stored for up to 72 h in a preservation solution with and without glutathione. We found that adding glutathione to the preservation solution slowed the rate of loss of glutathione from the cells. These data suggest that at hypothermia the cell may be permeable to GSH. Methods to suppress the loss of glutathione during preservation of organs may be an important factor in suppressing oxygen free radical injury.
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PMID:Effect of cold storage on tissue and cellular glutathione. 207 Jun 16

The effects of cold-restraint as a physiological stressor on the glutathione (GSH) content of the liver and other tissues were examined in male mice. Mice of the ICR, NIH, ND/4, and B6C3F1 strains subjected to cold-restraint for 2 or 3 h experienced a loss of hepatic GSH concentrations ranging from approximately 15 to 50%. Though 3 of these strains (ICR, NIH, and B6C3F1) experienced hypothermia as result of the cold-restraint treatment, with average decreases in core body temperature ranging from 3.3 to 9.8 degrees C, hepatic GSH levels were depressed in the ND/4 mouse in the absence of changes in core body temperature. The ability of cold-restraint as a stressor to diminish hepatic GSH therefore could not be attributed simply to hypothermia. The decrease in hepatic GSH from cold-restraint in ND/4 mice was paralleled by a decrease in non-protein sulfhydryl (NPSH) content of the liver. In addition to its effects on liver GSH and NPSH concentrations, 1.5 h of cold-restraint stress significantly depressed plasma, heart, kidney, and lung NPSH concentrations. The extent of NPSH depression was equivalent to the GSH depression in the liver, heart, and kidney, despite the observation that the normal contribution of GSH to total NPSH content in these tissues ranged from a high of 89% (liver) to a low of 49% (heart). These results with cold-restraint in the ND/4 mouse suggest that other stressors may significantly depress cellular concentrations of GSH and other thiols, and may thereby render the affected tissues more susceptible to the toxicity of free radicals, electrophilic xenobiotic metabolites, or reactive oxygen species.
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PMID:Depression of glutathione by cold-restraint in mice. 231 51

Organ culture of murine thyroid allografts in hyperbaric oxygen (95% O2 at 25 psi, 37 degrees C) for 48 hr, results in prolonged allograft survival. Endocrine tissues can be cultured at 37 degrees C--however, this method may not be applicable to vascularized organs at normothermia. The aim of this study was to apply hyperbaric oxygen culture (HOC) under organ preservation conditions (hypothermia, UW solution) that have been shown to be successful in clinical organ transplantation. B10BR/SGSNJ murine thyroid lobes were transplanted beneath the kidney capsule of C57BL/10J recipients. Thyroids were cultured in Eagle's MEM at 37 degrees C (controls) and at 5 degrees C, under hyperbaric conditions (95% O2:5% CO2, 25 psi). Alternatively, thyroids were cultured in UW solution (+/- allopurinol/GSH) at 5 degrees C, for up to 7 days. Graft survival was determined 21 days posttransplant by 125I uptake and by histology. In Eagle's MEM, HOC at 37 degrees C/48 hr and 5 degrees C/7 days, resulted in 93% and 20% allograft survivals, respectively. In UW solution (- allopurinol/glutathione [GSH]), HOC at 5 degrees C/7 days resulted in 83% allograft survival: immunoperoxidase staining showed a decrease of MHC class I alloantigen expression. Oxygen free radical scavenger (allopurinol/GSH) addition to the UW solution diminished this effect and suggested an oxygen free radical-mediated mechanism in immunoalteration. These results demonstrate that HOC for 7 days reduced the antigenicity and immunogenicity of murine thyroid grafts under conditions that simulate organ preservation. Hypothermic hyperbaric oxygen culture conditions require testing in a higher animal species and in vascularized grafts to determine if this method can be applied to whole-organ transplantation.
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PMID:Prolonged survival of murine thyroid allografts after 7 days of hyperbaric organ culture in the UW preservation solution at hypothermia. 233 13

In the feline intestine studies have implicated superoxide (O.-) and other oxygen derived free radicals as initiators of injury as measured by increased capillary permeability during the reperfusion period. Biochemical mechanisms of this free radical generation include: xanthine oxidase dependent O.- production, hydrogen peroxide (H2O2) formation by superoxide dismutase (SOD), hydroxyl radical (OH-) production via the Haber-Weiss reaction, and lipid radical formation from membrane peroxidation. Pathological consequences of these events include inflammatory neutrophil infiltration, damage to the collagen and mucosal basement membrane, increased capillary permeability, edema, cell degeneration and necrosis. Animal models of neonatal necrotizing enterocolitis (NNEC) indicate that intestinal injury occurs after the etiologic factors (hypothermia, hypoxia) are removed. In order to determine the role of active oxygen species in the pathogenesis of NNEC, weanling hamsters and neonatal piglets were cold stressed and activities of pro/antioxidant enzymes were determined, and histopathologic and ultrastructural studies were performed. Cold stressed weanling hamsters showed a 55.7% (P less than 0.05) decrease in xanthine dehydrogenase/xanthine oxidase activity ratio. Light microscopy revealed scattered colonic mucosal erosions and submucosal edema in 50% of cold stressed animals. Transmission electron microscopy demonstrated degeneration of colonic mucosal epithelial cells, enlarged intracellular spaces, cytoplasmic vacuolization, and nuclear membrane swelling. The colonic serosa was also edematous and infiltrated with bacteria. Large intestinal tissue from cold stressed neonatal piglets showed a significant increase (P less than 0.05) in Mn and Cu, Zn, SOD, CAT, GSH-Red, total GSH, and Glc6-PD at 0 and 12 hrs. post stress.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Intestinal post-ischemic reperfusion injury: studies with neonatal necrotizing enterocolitis. 259 24

A series of studies were conducted in order to further characterize the previously reported effect of morphine to diminish hepatocellular concentrations of glutathione (GSH) in mice. Naive ICR mice administered morphine (i.p.) in doses up to 1000 mg/kg had diminished hepatic GSH concentrations, with a maximum depletion of approximately 50% occurring at doses of 250 mg/kg or greater. No such effect from an acute challenge with morphine was observed in morphine-tolerant mice. The intracerebro-ventricular administration of the opioid receptor antagonist naltrexone (250 micrograms) completely blocked the hepatic GSH depression resulting from the systemic (i.p.) administration of morphine (100 mg/kg). When morphine (100 micrograms) was administered by the i.c.v. route, GSH concentrations in liver and plasma were significantly altered while heart and kidney were unchanged. Variable responses to i.c.v. morphine were obtained in spleen, stomach and lung. The depression of hepatic GSH was found not to be a consequence of morphine-induced hypoxia or hypothermia, and could not be attributed to intracellular oxidation of GSH.
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PMID:Perturbation of glutathione by a central action of morphine. 275 29

The effects of co-administration of reduced glutathione (GSH) on the lethality of sodium selenite (SS) and on SS-induced hypothermia and hyperphagia were examined in adult male ICR mice. Tissue GSH levels after s.c. injection were also determined. In the plasma, GSH concentration was significantly elevated up to 2 h after injection of 2 mmol/kg of GSH. Little change was observed in liver, and erythrocyte levels, the lethality of SS was enhanced by a similar dose of GSH. This enhancement, however, was observed only when SS was injected during the period when plasma GSH was elevated. These results suggest that the interaction between GSH and SS in plasma was the major contributor to the enhancement of SS toxicity. Hypothermia induced by SS was also enhanced by a 60-fold dose of GSH but not by a 6-fold dose of GSH. With respect to hyperphagia, GSH suppressed the effect of SS, probably because of depressing effect of co-administration of SS an GSH.
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PMID:Modification of lethal, hypothermic and hyperphagic effects of sodium selenite by reduced glutathione in mice. 317 27

The responses of fed, fasted, and hyperthyroid (T4) Sprague-Dawley male rats to 50 mg 1,1-dichloroethylene (1,1-DCE)/kg were compared. Hyperthyroid rats received three sc injections of thyroxine (100 micrograms/100 g) at 48-hr intervals; all other rats were sham-injected. 1,1-DCE was given po in mineral oil 24 hr after the last T4 dose; controls received only mineral oil. Animals were killed at 2, 4, and 8 hr. Liver GSH contents were lowered about 55% by both fasting and T4 while GSH transferase activities were lowered about 20% by fasting and 35% by T4. Only T4 pretreatment lowered alcohol dehydrogenase activities. Liver injury (i.e., serum glutamate pyruvate transaminase, histology) after 1,1-DCE was minimal in fed rats, moderate in fasted rats, and intermediate in T4 rats. Fasted rats showed a more pronounced depletion of liver GSH after 1,1-DCE than T4 rats and only in fasted rats did the toxicant decrease activities of the detoxification enzymes. Hypoglycemia after 1,1-DCE occurred in fed rats, but more rapidly in T4 rats. In contrast, fasted rats unexpectedly became hyperglycemic after the toxicant. Patterns of body temperature change after the toxicant, which might be due to its metabolites, were dissimilar. Hypothermia was not observed in fed rats, was only transiently evident in T4 rats, but occurred rapidly within 1 hr in fasted rats and steadily became more severe. The dissimilar patterns of liver enzyme and body temperature and serum glucose change after the toxicant in the three groups are indicative of different pathways of injury potentiation by fasting and hyperthyroidism.
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PMID:Potentiation of 1,1-dichloroethylene hepatotoxicity: comparative effects of hyperthyroidism and fasting. 341 96

The alpha, beta-unsaturated carbonyl compound diethylmaleate (DEM) depletes glutathione (GSH) from liver and other tissues, and for this reason it is often used in toxicological research to study the GSH-mediated metabolism of xenobiotics. In addition to GSH depletion, however, DEM has been shown to have other nonspecific effects, such as alteration of monooxygenase activities or glycogen metabolism. In this study we found that DEM (1 ml/kg) inhibited protein synthesis in brain and liver, following in vivo administration to mice. Protein synthesis was measured as the incorporation of [3H]valine into trichloroacetic acid-precipitable material. Administration of DEM also decreased body temperature by 2-3 degrees. By increasing the environmental temperature from 22 degrees to 35 degrees the hypothermic effect of DEM was prevented, without affecting its ability to deplete GSH from brain and liver. Furthermore, when mice were maintained at 35 degrees, DEM still caused a significant decrease in protein synthesis, suggesting that this effect was only partially due to hypothermia. To test whether inhibition of protein synthesis was related to GSH depletion, groups of animals were dosed with the alpha, beta-unsaturated carbonyl phorone (diisopropylidenacetone) or the specific inhibitor of GSH synthesis, buthionine sulfoximine (BSO). Phorone decreased GSH in liver and brain; however, it had no effect on protein synthesis. BSO decreased GSH levels in liver and kidney, but not in brain, and did not have any effect on protein synthesis in any of these tissues, nor did it cause any hypothermia. Furthermore, when hepatic GSH content was decreased by in vivo administration of DEM or BSO, there was no inhibition of protein synthesis measured in vitro. These results indicate that, at the dose normally used to deplete GSH from various tissues. DEM also exerts an inhibitory effect on protein synthesis, which appears to be only partially due to its hypothermic effect, and is independent from GSH depletion. BSO, which, in our experimental conditions, lacks this and other nonspecific effects, might be a good alternative for studies aimed at characterizing the role of GSH in the metabolism and toxicity of chemicals.
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PMID:Effect of diethylmaleate and other glutathione depletors on protein synthesis. 376 26

In male mice of ddY strain, a single dose of 1,1-dichloroethylene (1,1-DCE, 0.1 ml/kg, ip) produced severe renal damage at 24 hr, as evidenced by elevations in plasma urea nitrogen concentration and kidney calcium content and by massive renal tubular necrosis, while hepatic damage was less severe. A precipitous decrease in body temperature started as early as 30 min after administration of 1,1-DCE and lasted for 24 hr. Glutathione concentrations decreased in the liver and kidney, with a rebound increase seen in the former but not in the latter tissue. In carbon tetrachloride-poisoned mice, the renal toxicity of 1,1-DCE was markedly potentiated. Pretreatment with either diethyldithiocarbamate (DTC) or carbon disulfide (CS2) blocked all of these 1,1-DCE-induced toxic manifestations in normal and carbon tetrachloride-poisoned mice. Both agents, however, did not prevent the hypothermia induced by monochloroacetic acid or chloroacetyl chloride, proposed active metabolites of 1,1-DCE. Since DTC and CS2 inhibited hepatic and renal microsomal drug metabolizing enzyme activities (Masuda and Nakayama, 1982, 1983), it is probable that the protective action of DTC and CS2 against renal and hepatic injury induced by 1,1-DCE may be due to an inhibition of the metabolic activation of 1,1-DCE to its proposed epoxide in each organ. The action of DTC given po may be mediated by CS2 produced in the stomach. The hypothermia induced by 1,1-DCE may not result from a direct action of 1,1-DCE per se, but by its metabolites.
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PMID:Protective action of diethyldithiocarbamate and carbon disulfide against acute toxicities induced by 1,1-dichloroethylene in mice. 631 3

The hepatobiliary transport of glutathione (GSH) and methylmercury (MM) was investigated in male and female rats anesthetized with pentobarbital sodium. When bile flow was altered with either sodium dehydrocholate (DHC), hypertonic sucrose infusion, or by hypothermia, the absolute rates of GSH and MM secretion into bile were not affected, resulting in parallel concentration changes in the bile fluid for both GSH and MM. Indocyanine green and sulfobromophthalein (BSP), but not BSP-glutathione complex, inhibited the biliary secretion of free GSH. This inhibition was accompanied by a parallel inhibition of MM secretion into bile and occurred without any changes in liver GSH or MM levels. On the other hand, the intravenous administration of cysteine, GSH, and penicillamine was associated with an increase in the secretion rate of reduced sulfhydryl groups into bile and an increase in the biliary secretion rate of MM. The increased biliary secretion rate of MM after phenobarbital pretreatment was also associated with an increased rate of secretion of GSH into bile. In addition, sex differences and individual variability in the biliary secretion of MM were correlated with differing abilities to secrete GSH into bile. The results suggest the presence of a biliary transport system for GSH that determines the biliary secretion of MM.
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PMID:Biliary transport of glutathione and methylmercury. 683 49


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