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)

Hyperplastic nodular cirrhosis was induced in rats by long-term (6 month) i.p. administration of thioacetamide at doses of 2.66 mmol/kg body wt, three times per week. The survival rate of animals at the end of the treatment was 90%. To follow the temporal changes samples at 0, 7, 15, 30, 45, 60, 90, 150 and 180 days from rats during thioacetamide intoxication and from chronological controls were obtained. The cirrhogenic ability of this treatment was assessed on the basis of morphological changes: the development of macronodular cirrhosis and the appearance of fibrous septa of collagen through portal spaces. Parameters of liver injury and cholestasis were obtained by assaying the serum activities of isocitrate dehydrogenase and gamma-glutamyltransferase. Enzymes and metabolites related to glutathione redox systems, as well as other antioxidant enzymes, were tested. Catalase and glutathione peroxidase, the two enzymes involved in the elimination of peroxides, and glutathione reductase decreased significantly at the end of the 6 months of intoxication, while Cu-Zn and Mn superoxide dismutases increased progressively during the long-term thioacetamide treatment. Protein thiol levels profile showed a biphasic change increasing from the 7th day and were insensitive to the 30% depletion of intracellular glutathione (GSH). To study the relationship of the intracellular thiols on the mechanisms of cell proliferation and differentiation during the cirrhogenic process, DNA content was assayed by flow cytometry in isolated hepatocytes, and DNA ploidy and distribution between G0-G1, S and G2 + M phases were determined. Remarkable changes in relation to a sharp increase in diploid population from 7 to 180 days (24.5%-->85.5%), a pronounced decrease in polyploid populations (tetraploid+octoploid) in the same period (73.7%-->12.3%), and elevations in the populations in S phase (S1 + S2) were observed in thioacetamide-treated rats. The results obtained indicate that hepatocytes isolated from thioacetamide-treated rats showed a marked tendency to diploidy, an enhancement in DNA replication parallel to the hepatic content of protein sulphydryl groups and a significant decline in antioxidant enzyme activities. The increase in protein thiols was independent of GSH level and of the thiol redox state.
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PMID:Relationship between antioxidant systems, intracellular thiols and DNA ploidy in liver of rats during experimental cirrhogenesis. 761 93

Manganese superoxide dismutase (MnSOD) levels were monitored as a function of time in culture to determine whether these levels were altered at logarithmic growth versus when the cells exhibited density limitation of growth. For comparison, activities of the antioxidant enzymes copper, zinc superoxide dismutase (CuZnSOD), catalase, and glutathione peroxidase were also evaluated. Four cell lines were studied, two of which exhibited density limitation of growth and two of which did not. Each cell line showed a unique antioxidant enzyme profile. The two cell lines that showed density limitation of growth also demonstrated induction of MnSOD at the time when the cells stopped proliferating in culture, whereas the other two cell lines did not show induction of MnSOD. There was no strict correlation between density limitation of growth and activities of the other antioxidant enzymes. To determine whether SOD varied with various phases of the cell cycle, NIH/3T3 cells were synchronized using serum starvation, and then SOD activities were measured during quiescence (G0) and the phase of DNA synthesis (S-phase). MnSOD was decreased during S-phase compared with G0, whereas CuZnSOD was increased during S-phase compared with G0, demonstrating alteration of SOD activities with varying phases of the cell cycle. This study suggests the possibility that increased MnSOD may correlate with decreased cell proliferation and suggests significant alterations in SOD activities during the cell cycle.
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PMID:Antioxidant enzyme levels as a function of growth state in cell culture. 763 59

The effects were examined of 6-month intermittent hypobaric (4000 m) exposure on the antioxidant enzyme systems in soleus and tibialis muscles of rats. At the end of the 6-month experimental exposure, the six rats in both the exposed group and the control group were sacrificed. Immunoreactive mitochondrial superoxide dismutase (Mn-SOD) contents were measured as well as the activities of antioxidant enzymes [Mn-SOD, cytosolic SOD (Cu,Zn-SOD), catalase (CAT), and glutathione peroxidase (GPX)]. Thiobarbituric acid-reactive substances (TBARS) were also determined as an indicator of lipid peroxidation. The high altitude exposure resulted in a marked increase in TBARS content in soleus muscle, suggesting increased levels of oxygen free radicals. Conversely, significant decreases in both Mn-SOD content and activity in soleus muscle were noted after exposure. Such trends were not noticed in tibialis muscle. On the other hand, no significant changes in Cu,Zn-SOD, CAT, or GPX were observed in either muscle. These results suggested that the increases in lipid peroxidation were most probably a result of decreased Mn-SOD function which was more depressed in oxidative than in glycolytic muscle.
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PMID:Oxidative stress induced by intermittent exposure at a simulated altitude of 4000 m decreases mitochondrial superoxide dismutase content in soleus muscle of rats. 787 34

Peroxidative tissue damage has been reported to contribute to several pathological disorders. Despite high exposure to both exogenous and endogenous oxidant stress, the strong cell defence mechanism of the gastric mucosa protects mucosal epithelial cells against these noxious stimuli. However, some environmental factors involved in lipid peroxidation (such as cadmium), which disrupt gastric mucosal protection, may impair the mucosal barrier and facilitate the occurrence of gastric ulcers. In an experimental study to investigate this hypothesis, the level of cadmium-induced lipid peroxidation products (TBARS) and an antioxidant enzyme (SOD) were investigated. The mucin content (P < 0.01) and prostaglandin levels (P < 0.05) of mucosa as components of the gastric mucosal barrier were found to be significantly reduced in rats exposed to 15 ppm of cadmium in water for 30 days when compared with those of unexposed controls. TBARS levels in blood (P < 0.05) and mucosa (P < 0.001) increased markedly in cadmium-exposed animals whereas blood SOD levels remained unchanged. The significant correlation between TBARS and mucosal cadmium (r = 0.664, P < 0.01), as well as between cadmium and PGE2 (r = -0.719, P < 0.01), led to the conclusion that cadmium-induced lipid peroxidation is involved in the increased vulnerability of gastric mucosa to injurious stimuli in rats. This susceptibility may be responsible for the high incidence of stress-induced gastric ulcer in the population.
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PMID:Role of lipid peroxidation in cadmium-induced impairment of the gastric mucosal barrier. 792 76

The rise in antioxidant enzyme activity in the lungs of late-gestation fetuses is thought to be caused by the preparation of the pulmonary antioxidant system for birth. However, recent data have shown that such a rise also occurs in the livers of late-gestation fetuses. Consequently, this surge cannot solely be ascribed to the preparation of the pulmonary antioxidant system for birth. In this study we examine the expression of copper/zinc superoxide dismutase (Sod1) and glutathione peroxidase (Gpx1) in various organs of late-gestational mouse fetuses. Furthermore, we compare the expression of these genes in organs of fetuses, neonates, and adult mice. These studies were carried out to investigate whether the change in mRNA levels for these two genes is related to a developmental change in oxidant stress. Our data demonstrate that an increase in both Sod1 and Gpx1 mRNA occurs in lungs and livers of late-gestational mouse fetuses. The brain demonstrates an increase in Sod1 expression at or around the time of birth, the kidney shows an elevation in Gpx1 mRNA levels, and the heart fails to demonstrate a surge in both Sod1 and Gpx1 mRNA levels. Our data show that the liver is the organ with the highest levels of Sod1 and Gpx1 mRNA in embryos and neonates (immediately after birth). In the adult, the liver has the highest levels of Sod1 mRNA and the spleen the highest level of Gpx1 mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Expression of copper/zinc superoxide dismutase and glutathione peroxidase in organs of developing mouse embryos, fetuses, and neonates. 816 54

Seven beagle dogs were administered sucrose (control animals) or different doses of (-)deprenyl orally by means of capsules for 3 weeks. Activities of Cu Zn-SOD and Mn-SOD were determined in striatum and hippocampus in these animals. There was a significant dose-dependent increase in activities of total as well as in both types of SOD enzymes in striatum but not in hippocampus. The results suggest that this monoamine oxidase B inhibitor can increase antioxidant enzyme activities in striatum but not in hippocampus in the dog, thus showing brain region selectivity. These results are in accordance with previously published observations in rats.
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PMID:(-)Deprenyl increases activities of superoxide dismutase (SOD) in striatum of dog brain. 819 23

Free radical-initiated lipid peroxidation (LP) following intestinal ischemia/reperfusion (I/R) may disrupt mucosal integrity. It is unknown if inhibition of LP prevents this injury. We analyzed rat ileum, subjected to I/R, for evidence of LP inhibition and structural damage following treatment with the 21-aminosteroid, U74389F, a potent LP inhibitor. Four groups of Lewis rats were studied after superior mesenteric artery occlusion with ligation of collateral arcades: (i) no ischemia, (ii) 10 min ischemia, (iii) 10 min ischemia + 1 hr reperfusion, (iv) 10 min ischemia + 1 hr reperfusion + U74389F (6 mg/kg i.v. prior to clamp removal and reperfusion). Ileal mucosa was analyzed for: 9i0 superoxide dismutase (SOD; U/mg protein), a key antioxidant enzyme, (ii) myeloperoxidase (MPO; U/mg protein), an index of PMN stimulation, (iii) malondialdehyde (MDA; pmole/mg), an end product of LP, and (iv) routine histology. MDA rose from 2.09 +/- 0.44 (mean +/- SE) in Group 1 to 15.10 +/- 2.22 in Group 3 following I/R (P < 0.01). In Group 2 and Group 4, MDA remained unchanged at 3.25 +/- 1.38 and 1.73 +/- 0.15, respectively. MPO, likewise, rose during I/R from 0.59 +/- 0.17 in Group 1 to 1.10 +/- 0.13 in Group 3 (P = 0.08) and 1.49 +/- 0.24 in Group 4 (P < 0.05). SOD did not vary significantly in the four groups studied. Despite PMN stimulation indicated by increased MPO with reperfusion, no PMN infiltration was seen histologically. U74389F normalized MDA, indicating effective inhibition of LP; however, similar epithelial sloughing and edema and hemorrhage in the lamina propria were seen in treated and untreated rats. These data implicate MDA-independent or possibly LP-independent pathways in intestinal morphologic damage occurring with I/R.
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PMID:Inhibition of intestinal lipid peroxidation does not minimize morphologic damage. 823 Nov 75

We quantitated the ability of intratracheally administered liposome-encapsulated antioxidant enzymes to reduce reactive oxygen species injury to the pulmonary microvasculature. Cationic liposomes containing 3,500 U of Cu,Zn superoxide dismutase (Cu,Zn SOD) and 3,124 U of catalase were instilled into rabbits. The animals were killed 2-72 h later and their lungs were removed and perfused with Krebs Ringer with 5% wt/vol of fat-free bovine serum albumin. The pulmonary filtration co-efficient (Kf,c) was measured before and after adding 500 microM xanthine and 5 mU/ml xanthine oxidase (XO) into the lung perfusate. Two hours after a single intratracheal instillation of liposome-entrapped Cu,Zn SOD and catalase, lung antioxidant enzyme activities were 34 and 125% higher than the corresponding control values, remained virtually unchanged for up to 8 h post-instillation, and then decreased, reaching baseline values between 24 and 72 h. Addition of xanthine and XO into the lung perfusate of un-instilled rabbits, or rabbits that received liposomes with inactivated enzymes, caused a 100% increase in Kf,c (control value: 2 +/- 0.12 ml.min-1 x cmH2O-1 per 100 g dry lung weight). On the other hand, Kf,c values of rabbits lungs instilled with liposome-encapsulated active Cu,Zn SOD and catalase and challenged with xanthine and XO 8-24 h later remained at baseline levels. Instillation of liposomes containing either enzyme was equally effective in preventing the increase in Kf,c, indicating that both superoxide anions and hydrogen peroxide were necessary for the initiation of injury. We concluded that intratracheal instillation of liposome-encapsulated antioxidant enzymes caused a transient increase of lung antioxidant enzyme levels which protects the pulmonary microvasculature from free radical-initiated injury.
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PMID:Mitigation of oxidant injury to lung microvasculature by intratracheal instillation of antioxidant enzymes. 823 68

Dexamethasone (10 mg/kg/day) or vehicle was administered in a randomized, controlled fashion to 3-day preterm guinea pigs exposed to either 21% oxygen or 95% oxygen for 72 hr and maintained in room air for a further 96 hr. Treatment with dexamethasone had no effect on survival of preterm pups maintained in either 21% or 95% O2. Dexamethasone treatment reduced the growth rate of pups, the effect occurring earlier (0-3 days) in 21% O2-treated pups than in 95% O2-treated pups (5-7 days). Exposure to 95% O2 reduced the survival rate of preterm animals (73% vs 100%, P < 0.05). Surviving pups developed acute lung injury, characterized by the accumulation of a protein-rich exudate in the alveoli and an infiltration of inflammatory cells, particularly neutrophils into the lung. Dexamethasone treatment attenuated the pulmonary inflammatory cell infiltration, in particular neutrophils, both during oxygen exposure (16.4 x 10(4) vs 9.4 x 10(4)/mL; P < 0.05) and following return to ambient conditions (28.0 x 10(4) vs 5.1 x 10(4)/mL; P < 0.05). Elastase activity in bronchoalveolar lavage fluid, which was primarily of neutrophil origin, was unchanged by dexamethasone treatment. Dexamethasone-treated pups had increased pulmonary antioxidant enzyme activities (Cu/Zn-superoxide dismutase; Mn-superoxide dismutase, catalase and glutathione peroxidase) during recovery from oxidative injury. Although there was both a marked reduction in numbers of neutrophils in the lung and elevated pulmonary antioxidant enzyme activities in dexamethasone-treated pups, the degree of microvascular permeability, as determined by both the lung wet weight/dry weight ratio and the presence of plasma proteins in the lavage fluid, was unchanged. Combined, these results imply that dexamethasone, although capable of blunting the influx of neutrophils to the hyperoxia-exposed lung and inducing antioxidant defences in the immature lung, cannot modify the progression of acute oxygen-induced injury of the immature lung.
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PMID:Dexamethasone treatment fails to reduce oxygen-induced lung injury in the preterm guinea pig. Effects on pulmonary inflammation and antioxidant status. 824 Apr 12

The time course and nature of the pulmonary inflammatory and antioxidant responses, both during and after hyperoxic-induced acute lung injury were studied in the preterm guinea pig. Three-day preterm (65 days gestation) guinea pigs were randomly exposed to either 21% O2 (control) or 95% O2 (hyperoxia) for 72 hours. All pups were then maintained in ambient conditions for up to a further 11 days, during which time lung damage was monitored. In animals exposed to hyperoxia, evidence of acute lung injury and inflammation was characterized by a marked increase in microvascular permeability and elevated numbers of neutrophils in bronchoalveolar lavage fluid. Protein concentration, elastase-like activity and elastase-inhibitory capacity in lavage fluid were at a maximum at the end of the 72 hours hyperoxic exposure. Four days later, all values had returned to control levels. In contrast, increased numbers of neutrophils, macrophages and lymphocytes were recovered in the lavage fluid during this early recovery period. Coinciding with the influx of inflammatory cells, there was a significant increase in glutathione peroxidase, manganese superoxide dismutase and catalase activities in immature lung. Lung copper/zinc superoxide dismutase activity remained unchanged during both experimental periods. The strong temporal relationship between the influx of inflammatory cells to the lung and the induction of pulmonary antioxidant enzyme defences suggests that a common mechanism underlies both responses. These findings have led us to regard inflammation in the hyperoxic-injured immature lung as a beneficial event and not, as previously suggested, as part of the injurious process.
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PMID:Temporal association between pulmonary inflammation and antioxidant induction following hyperoxic exposure of the preterm guinea pig. 837 May 48


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