Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30044 (antioxidant enzyme)
 8,037 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Small dosages of endotoxin (100--500 micrograms/kg) provide significant protection against the acute manifestations of pulmonary O2 toxicity and lethality. Ninety-seven percent of endotoxin-treated adult rats survived a 72-h exposure to greater than or equal to 95% O2 with mimimal lung changes, compared to 32% of control animals (P less than 0.01). Exposure to greater than or equal to 95% O2 for 7 days resulted in a 20% survival rate in untreated control rats vs. 98% survival in endotoxin-treated rats (P LESS THan 0.01). Histological evaluation of lung from survivors revealed substantially less collagen and reticular fiber deposition in the endotoxin-treated animal lungs. Endotoxin treatment was associated with increased activity of the protectant antioxidant enzyme systems of the lung in an apparent dose-response manner. Endotoxin's protective activity against O2 toxicity does not appear to depend on an initial toxic insult to the lung like with alpha-naphthylthiourea, oleic acid, or alloxan treatment. The data support a protective role for endotoxin against the acute and the more chronic manifestations of O2-induced pulmonary injury.
J Appl Physiol Respir Environ Exerc Physiol 1979 Sep
PMID:Endotoxin protection against oxygen-induced acute and chronic lung injury. 53 52

Undernutrition may exacerbate hyperoxia-induced lung injury, a finding that may be of significance in the early clinical management of the premature human infant. Addressing this specific problem, we found that 72 h of food restriction in guinea pig pups delivered 3 days preterm increased mortality rates among pups exposed to 95% oxygen (8/18) and yet had no effect on 21% oxygen (air)-exposed pups (0/10). Reduced tolerance of hyperoxic conditions was not, however, associated with increased lung injury, assessed as pulmonary microvascular leakage. Pulmonary antioxidant enzyme activities [Cu,Zn superoxide dismutase (SOD), Mn SOD, glutathione peroxidase, and catalase] were unaltered by starvation or hyperoxia. Lung glutathione concentration was slightly decreased after food restriction, whereas hyperoxic exposure did not change either lung or bronchoalveolar lavage fluid glutathione concentrations or lung antioxidant enzyme activities. Increased susceptibility to the lethal effects of oxygen in the starved preterm guinea pig pup could not be attributed to a deficiency of pulmonary antioxidant defenses.
Am J Physiol 1992 Sep
PMID:Effect of food restriction on hyperoxia-induced lung injury in preterm guinea pig. 141 61

Enzyme activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) were determined in the liver as well as several specific brain regions of young and old Fischer-344 rats of both sexes. In the liver of male rats, activities of CAT as well as Mn-SOD were lower, while activities of Cu Zn-SOD were higher in old (30-month-old) rats than in young (7-month-old) ones. Activities of total SOD as well as GSH Px were comparable for young and old male rat livers. In contrast to male rats, in female rat livers, activities of CAT were significantly higher in old (28-months-old) rats, while activities of Mn-SOD were slightly (but significantly) higher in old rat livers. In old male rats, activities of Mn-SOD were significantly higher than in young males in several specific regions of the brain (the substantia nigra (s. nigra), striatum, hippocampus) but lower in the cerebellum. In particular, SOD activities in s. nigra, striatum and hippocampus in old male rats were several fold higher than corresponding values in young male rats. Activities of Cu Zn-SOD were generally unchanged with age. Activities of CAT as well as GSH-Px (both Se-dependent and non-Se-dependent forms) were also relatively unaffected by age. In female rat brains, activities of Mn-SOD as well as those of others all remained mostly unaffected by aging, although there was a general tendency of slightly higher activities in most cerebral regions for Mn-SOD in old female rats. Thus, age-related changes of these antioxidant enzymes in the liver and brain are markedly sex dependent and some enzyme activities (such as CAT in the liver) change in an opposite direction with age. Changes of Mn-SOD in the brain were markedly region-specific in male rats. Results suggest that the significance of the changes of these antioxidant enzyme activities during aging needs to be carefully interpreted, taking into consideration the fact that changes are markedly variable depending on sex as well as the organs and brain regions examined.
Mech Ageing Dev 1992 Sep
PMID:Age-related changes in antioxidant enzyme activities are region and organ, as well as sex, selective in the rat. 143 48

Bacterial endotoxin has been shown to protect rats from lethal hyperoxia. The structure of endotoxin contains diphosphoryl lipid A (DPL) as the lipid backbone stripped of protein and polysaccharides. DPL is the component of the endotoxin molecule that has been demonstrated (in previous studies) to be responsible for the immunologic, mitogenic, pyrogenic, and lethal properties of endotoxin. Monophosphoryl lipid A (MPL) is a nonpyrogenic, nontoxic modification of the DPL molecule that retains its immunostimulatory and mitogenic properties. We hypothesized that DPL may be the actual active component of endotoxin that protects rats from lethal hyperoxia. We also hypothesized that the protection from hyperoxia that is afforded by the DPL component may be related to endogenous release of tumor necrosis factor alpha which should allow MPL to also be protective. To test these hypotheses, we performed a series of experiments in which rats were treated with endotoxin, DPL, MPL or vehicle and exposed to room air or hyperoxia. We found that DPL and endotoxin both protected rats from lethal hyperoxia, but MPL alone was not protective. Even though MPL was not protective, DPL and MPL both increased endogenous release of tumor necrosis factor alpha early after injection (peak DPL level, 3619 +/- 1500 pg/ml, peak MPL level, 4038 +/- 500 pg/ml). Protection in both the endotoxin- and DPL-treated animals was associated with increases in lung antioxidant enzyme activities. We concluded that DPL protect rats from hyperoxia but that MPL is not protective in spite of its immunostimulatory and mitogenic effects.
J Lab Clin Med 1992 Sep
PMID:Diphosphoryl lipid A protects rats from lethal hyperoxia. 151 89

The antioxidant enzyme activities, the lipid peroxidation level, the parameters of glutathione metabolism, and the proportion of haemoglobin oxidation products were determined during the symptom-free period of childhood bronchial asthma. A decreased catalase activity and a significantly reduced glutathione instability were demonstrated as compared to the controls. The results indicate that antioxidant protection of the haemoglobin molecule in asthmatic children is considerably decreased.
Clin Chim Acta 1991 Sep 30
PMID:Examination of the role of oxygen free radicals in bronchial asthma in childhood. 175 97

Antioxidant enzyme activities of cultured human foreskin fibroblasts, keratinocytes, and melanocytes from healthy black and Caucasian donors were measured and compared. Fibroblasts had more (p less than 0.05) peroxidase, catalase, glutathione peroxidase, and superoxide dismutase activity than keratinocytes. Keratinocytes had more (p less than 0.05) peroxidase, catalase, glutathione peroxidase, and superoxide dismutase activity than melanocytes. No differences in antioxidant enzyme activities were observed between the cells of any type taken from black or Caucasian people. Antioxidant enzyme activities may affect resistance to damage by oxidants induced by ultraviolet radiation and inflammation.
J Invest Dermatol 1991 Sep
PMID:Disparate antioxidant enzyme activities in cultured human cutaneous fibroblasts, keratinocytes, and melanocytes. 187 41

The effects of culture duration on primary cultured mouse hepatocyte antioxidant levels (superoxide dismutase, catalase, glutathione peroxidase, vitamin E, and glutathione) and susceptibility to glucose oxidase (GO)- and hydrogen peroxide (H2O2)-induced cell killing and lipid peroxidation were examined. Membrane fatty acid composition was also evaluated. Adult male B6C3F1/CrlBR mouse hepatocytes were isolated by collagenase perfusion of the liver and cultured on 60-mm plastic dishes in Leibovitz's L-15 medium supplemented with glucose (1 mg/ml), dexamethasone (1 microM), fetal bovine serum (10%, v/v), and gentamicin sulfate (50 micrograms/ml) for 0 hr (freshly isolated cells) to 96 hr. Hepatocyte toxicity (determined by lactate dehydrogenase release and lipid peroxidation) after a 2-hr exposure to GO (0.8-80 micrograms/ml) or H2O2 (1-5 mM) decreased with increased time in culture. This decreased hepatocyte sensitivity to GO and H2O2 toxicity was not related to antioxidant enzyme activity since superoxide dismutase, catalase, and glutathione peroxidase declined during the 96-hr culture period. In contrast, glutathione and vitamin E levels in the cultured hepatocytes rose to 274.9 +/- 8.3% and 220.6 +/- 18.6% of the levels in freshly isolated cells (129.6 +/- 11.5 nmol and 0.10 +/- 0.01 nmol per 10(6) hepatocytes, respectively). The percentage of polyunsaturated fatty acids in hepatocyte phospholipids and triglycerides decreased with culture duration while the percentage of oleic acid increased in esterified and free fatty acid pools after 2 hr in culture. Total fatty acids were not affected by time in culture. These results suggest that the decreased hepatocyte susceptibility to the toxic effects of hydrogen peroxide may have been due to elevations in cellular GSH and vitamin E levels and decreases in membrane polyunsaturated fatty acids. The data also indicate that hepatocytes in primary culture undergo changes in antioxidant levels and fatty acid composition that may affect free radical toxicity at different times in culture.
Toxicol Appl Pharmacol 1989 Sep 15
PMID:Effects of culture duration on hydrogen peroxide-induced hepatocyte toxicity. 278 69

We investigated the possible involvement of reactive oxygen radical-related processes in chronic (12-wk) diabetes induced in rats by streptozocin (STZ). Diabetes was associated with significantly increased activities of catalase (CAT), glutathione reductase (GSSG-RD), and CuZn-superoxide dismutase (SOD) in the pancreas and of CAT and GSSG-RD in the heart. On the other hand, the liver of diabetic rats showed a generalized decrease in CAT, glutathione peroxidase (GSH-PX), and SOD as well as in the levels of reduced glutathione (GSH). Diabetic kidney also showed decreases in CAT and SOD, but the activities of GSH-PX were increased. Insulin treatment (9-12 U/kg body wt) that was started after 8 wk of diabetes and continued for 4 wk reversed all of the foregoing alterations in tissue antioxidant status. Our results suggest the presence of increased oxidative stress in uncontrolled diabetes as manifested by the marked alterations in tissue antioxidant enzyme activities, the magnitude of which increased with the degree of emaciation. The complex patterns of changes observed in the various tissues examined are believed to be the result of compensatory increases in enzyme activities (usually involving enzymes whose activity in control tissues is low) and direct inhibitory effects, possibly resulting from an increased tissue-oxidant activity. Our findings support the view that tissue antioxidant status may be an important factor in the etiology of diabetes and its complications.
Diabetes 1987 Sep
PMID:Alterations in free radical tissue-defense mechanisms in streptozocin-induced diabetes in rat. Effects of insulin treatment. 330 71

The administration of very low doses of bacterial endotoxin protects rats during exposure to hyperoxia and is associated with the induction of lung antioxidant enzyme activities. Copper-deficient rats have increased susceptibility to O2 toxicity, which may be related to their decreased lung superoxide dismutase activity (SOD) or decreased plasma ceruloplasmin concentrations. To determine whether endotoxin can protect against hyperoxia in this susceptible model, we exposed copper-deficient and control rats to a fractional inspiratory concentration of O2 greater than 0.95 for 96 h after pretreatment with 500 micrograms/kg of bacterial endotoxin or phosphate-buffered saline (PBS). Mortality in the copper-deficient and control rats given PBS and exposed to O2 for 96 h was 100%. Copper-deficient rats died significantly earlier during the exposure than controls. No mortality occurred in either group treated with endotoxin and hyperoxia despite the decreased activity of copper-dependent enzymes in the copper-deficient rats. Copper-deficient rats treated with endotoxin and exposed to hyperoxia did increase lung Cu-Zn-SOD activity, but activity remained below levels found in air-exposed controls. Mn-SOD activity was found to be induced above air-exposed controls in the copper-deficient rats treated with endotoxin and exposed to hyperoxia. Hyperoxic exposure resulted in a marked increase in plasma ceruloplasmin concentrations in the control rats, but no increases in ceruloplasmin occurred in the copper-deficient animals. Endotoxin protects copper-deficient rats from hyperoxia despite their decreased lung Cu-Zn-SOD activity, and decreased plasma ceruloplasmin.
J Appl Physiol (1985) 1986 Sep
PMID:Effects of bacterial endotoxin on protecting copper-deficient rats from hyperoxia. 375 84

Endotoxin treatment in normal rats has a marked protective effect against O2 toxicity (J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 47: 577-581, 1979 and 51: 577-583, 1981), and endotoxin's protective action is associated with stimulation of the lung's enzymatic antioxidant defense system (superoxide dismutase, catalase, glutathione peroxidase, and glucose-6-phosphate dehydrogenase). Vitamin E-deficient animals are especially sensitive to hyperoxidant stresses, including pulmonary O2 toxicity. In these studies we tested whether endotoxin could reverse the increased susceptibility of vitamin E-deficient rats to hyperoxic challenge. We found that untreated vitamin E-deficient rats do succumb more readily to O2 toxicity [0/11 alive at 72 h in greater than 95% O2, lethal time for 50% of the animals (LT50) = 50 h] than rats fed a regular diet (4/14 alive, LT50 = 69 h). In contrast, 15 of 16 vitamin E-deficient rats treated with endotoxin survived the same O2 exposures (P less than 0.001) and showed significantly reduced pulmonary edema compared with the other groups. The endotoxin-treated vitamin E-deficient group was also the only one to demonstrate significant elevations of all the antioxidant enzymes during O2 exposure, suggesting that the antioxidant enzyme defenses of the lung have a more primary and important role in prevention of O2-induced lung injury than the lipid-associated antioxidant, vitamin E.
Am J Physiol 1984 Sep
PMID:Endotoxin treatment protects vitamin E-deficient rats from pulmonary O2 toxicity. 638 80


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