Red Cell Glutathione Peroxidase Research Articles

Asthma and oxidant stress: nutritional, environmental, and genetic risk factors.

A considerable body of evidence suggests that oxidant stress results in inflammation and tissue damage in the respiratory system, and later in immune damage, and that individuals with lowered cellular reducing capacity are at increased risk to develop asthma. Reducing capacity in the erythrocyte is generated through the pentose phosphate pathway and this pathway also generates a major portion of the reducing capacity in all cells of the body. Therefore, dietary, environmental, and genetic factors which diminish cellular reducing capacity will increase tissue vulnerability to oxidant stress and are likely to increase asthma risk. Dietary selenium deficiency lowers red cell glutathione peroxidase activity and is associated with an increased risk for asthma, and low dietary intakes of vitamins C and E also appear to increase asthma risk. High body iron stores increase free radical production and may also elevate asthma risk. Environmental lead exposure depresses the activities of a several enzyme systems that influence cellular reducing capacity (glucose-6-phosphate dehydrogenase, NAD synthetase, glutathione peroxidase, superoxide dismutase, catalase) and consequently may increase asthma risk. Genetically-determined low activity of glucose-6-phosphate dehydrogenase lowers cellular reducing capacity and may also heighten asthma risk. Simple dietary and environmental interventions may significantly reduce oxidant stress and prevent or minimize the development of asthmatic symptoms and should prove to be a cost effective approach to asthma management in addition to current pharmacological strategies.

Superoxide Anion Release by Polymorphonuclear Leukocytes in Whole Blood of Newborns and Mothers during the Peripartal Period

Superoxide anion (.O2-) production was investigated in whole blood of mothers in the peripartal period and in neonates. Blood samples from 14 mothers undergoing vaginal delivery (VD) were tested at the beginning of labor, during labor, after delivery, and 4 d after delivery. Nine mothers undergoing elective cesarean section (ECS) were tested before anesthesia, after extraction of the fetus, and 4 d later. Seventy-two healthy, full-term newborn infants were examined at birth and on the fourth day of life. Red cell glutathione peroxidase, catalase, glutathione reductase, and superoxide dismutase activities were also measured at birth and on the fourth day of life in 26 of the 72 neonates. Higher .O2- levels were detected in mothers undergoing VD compared with ECS (p < 0.05). A significant decrease was detected in zymosan-stimulated .O2- production between cord and fourth-day blood samples in both VD- and ECS-delivered infants (p < 0.01). Zymosan-stimulated samples showed higher values after VD than ECS, both in cord blood (p < 0.004) and on the fourth day of life (p < 0.006). A positive correlation was found between .O2- release in zymosan-stimulated cord blood and that found in the mothers at the beginning of labor (r = 0.654; p < 0.01), during labor (r = 0.721; p = 0.008), and after delivery (r = 0.832; p = 0.0008). A positive correlation was also found between .O2- release and glutathione peroxidase on the fourth day (r = 0.709, p = 0.014).(ABSTRACT TRUNCATED AT 250 WORDS)

Muscle enzymes in the diagnosis of ovine weaner nutritional myopathy

The diagnostic performance of plasma tests for muscle enzymes was measured in sheep from flocks affected by clinical and sub-clinical nutritional myopathy. Parallel combinations of tests for creatine kinase (CK), alanine amino transferase (ALT), aspartate amino transferase (AST) and lactate dehydrogenase had higher diagnostic sensitivity than CK alone. The enzymes ALT and AST showed the highest correlation with the degree of muscle damage. A parallel combination of tests for plasma CK and ALT as well as tests for plasma alpha-tocopherol and red cell glutathione peroxidase are recommended for the diagnosis of nutritional myopathy and a decision on the appropriate treatment. The number of false negative results based on a diagnosis from the microscopic examination of single muscles was higher than for the parallel combination of tests. The number of false negatives was highest for the vastus intermedius and lowest for the tensor fascia lata. Diagnosis using a panel of blood tests has the advantages of overcoming problems of inadequate muscle sampling, a larger number of sheep in the flock can be tested and a more rapid diagnosis can be obtained.

The relationship between micronutrient depletion and oral health in geriatrics

Changes in the oral microbial flora, some of which are related to mucosal disease, have been detected in the elderly, but the causes are not fully understood. This study has examined the possible role of micronutrient depletions in the reduced colonisation resistance and oral infection exhibited by some elderly subjects. The oral health, oral microbiology and micronutrient status of 37 geriatric patients aged 65-91 years (mean 81 years) were examined. Ten of the patients had no oral mucosal disease. Mucosal pathology in the remainder included erythema (27%), denture stomatitis (24%), angular cheilitis (16%) and atrophic glossitis (41%). Those with mucosal pathology had significantly lower serum iron concentrations (P = 0.02). Serum or plasma concentrations of zinc, copper, selenium, C-reactive protein, transferrin, caeruloplasmin, albumin, vitamin A and vitamin E were not significantly different between those with oral disease and those with healthy mouths. Similarly, activity of the selenium-containing enzyme, red cell glutathione peroxidase, did not differ significantly between the two groups. In both groups, plasma selenium concentrations (82%), red cell glutathione peroxidase activity (47%), plasma zinc concentrations (58%) and albumin concentrations (44%) tended to be below the lower limit of the reference interval. The influence of subclinical infection on these values is discussed.

Species-related variations in tissue antioxidant status—I. Differences in antioxidant enzyme profiles

1. 1. Antioxidants enzyme activity profiles in red cells of man, rabbit, quail, pig, and rat have been investigated and found to exhibit striking differences. 2. 2. No direct correlations between activities of “functionally coupled” enzymes (superoxide dismutase/ catalase and glutathione peroxidase/glutathione reductase) were apparent, suggesting their independent regulation. 3. 3. However, activities of red cell catalase and glutathione peroxidase in the various species studied were inversely correlated. 4. 4. This was most evident in quail red cells, which showed negligible catalase activity but the highest levels of glutathione peroxidase of all the species examined. 5. 5. A significant correlation between catalase and glutathione reductase activities was also demonstrated. 6. 6. This may be relevant to the suggestion that the binding of NADPH to catalase may serve to decrease the intracellular inactivation of this reducing cofactor which may be limiting in the glutathione reductase reaction. 7. 7. Basal levels of glutathione, which have been claimed to be limiting for the glutathione peroxidase reaction, were found to correlate positively with the activity of this enzyme in red cells. 8. 8. Myocardial tissues also exhibited species-related differences in antioxidant enzyme profiles but these did not bear any obvious relationship to patterns observed in the corresponding red cells.

Selenium and glutathione peroxidase levels in premature infants in a low selenium community (Christchurch, New Zealand).

By world standards, the selenium status of the adult population of Christchurch, New Zealand is low. To determine the status of infants undergoing neonatal intensive care, plasma and red cell selenium and glutathione peroxidase levels were measured in infants admitted to the regional neonatal unit. Plasma levels in all newborn infants were one third to one half those in adults. Premature infants had levels significantly lower than those in cord blood from term infants, but their levels were not different from those of term infants admitted to the unit. There were no differences between adult and infant red cell levels. The premature infants remaining in the neonatal unit showed dramatic decreases in plasma selenium and glutathione peroxidase with age, with many infants having selenium levels of less than 0.13 mumol/L (10 micrograms/L). Low levels were seen in infants fed orally as well as those on parenteral nutrition. Thus, the low selenium status of New Zealanders is associated with particularly low selenium levels in premature infants. Because these infants have a high risk for oxidative diseases such as bronchopulmonary dysplasia (chronic lung disease) and retinopathy of prematurity, the possibility that these conditions are more serious in the New Zealand population needs to be assessed and consideration given to dietary supplementation.

Red cell superoxide dismutase, glutathione peroxidase and catalase in down syndrome patients with and without manifestations of Alzheimer disease

The activities of red blood cell enzymes that scavenge the superoxide radical and hydrogen peroxide were measured in severely to profoundly retarded adult Down syndrome (DS) patients with and without manifestations of Alzheimer disease (AD), and control individuals matched for sex, age, and time of blood sampling. Cu,Zn superoxide dismutase (SOD-1) and glutathione peroxidase (GSHPx) activities were significantly elevated (1.39-fold and 1.24-fold, respectively) in DS individuals without AD. When an adjustment was made for the SOD gene dosage effect, DS patients with AD manifestations had significantly lower SOD levels than the matched control individuals. In contrast, DS patients with and without AD had a similar elevation in GSHPx (an adaptive phenomenon). The mean catalase (CAT) activity was no different in DS and control individuals; however, in a paired regression analysis, DS patients without AD had marginally lower CAT activity than control individuals, whereas DS patients with AD had slightly but not significantly higher CAT activity. Thus, AD manifestations in this DS population are associated with changes in the red cell oxygen scavenging processes.

Influence of selenium status in merino weaners on resistance to trichostrongylid infection

Weaned merino lambs, grazing pastures low in selenium, were used to investigate the effect of selenium status on immunity to trichostrongylids. Six weeks following selenium supplementation to 14 of the 27 sheep using intraruminal selenium pellets, 5000 Ostertagia circumcincta and 5000 Trichostrongylus colubriformis larvae were administered orally to all sheep. At four weeks after infection, the mean total worm burden in the selenium supplemented sheep (5537 +/- 343, n = 14) was not significantly different (P greater than 0.05) from that in the unsupplemented sheep (5614 +/- 374, n = 12) and faecal worm egg concentrations were also similar in the two treatment groups. At this time, mean red cell glutathione peroxidase activities in the supplemented and unsupplemented groups were 430 and 11 U g-1 haemoglobin, respectively, and clinical white muscle disease had been observed in the latter group. These results suggest that increasing selenium status of selenium deficient sheep by the use of intraruminal selenium supplementation, has a negligible effect on resistance to an artificial challenge infection of O circumcincta and T colubriformis.

Anthropological survey on red cell glutathione peroxidase (GPX1) polymorphism in central western Africa: a tentative hypothesis on the interaction between GPX1*2 and Hb beta *S allelic products.

Phenotype and allele frequencies for erythrocyte glutathione peroxidase (GPX1) polymorphism are reported in the Mbugu and Sango (Central African Republic), Goun (Benin), and Bamileke (Cameroon) ethnic groups. The GPX1*2 allele frequencies (from 0.012 in the Sango to 0.058 in the Bamileke) fit into the range of the data already known for the Subsaharan populations. The value of GPX1*2 for study of the genetic admixture between Negro and Pygmy populations is suggested. Three different unusual GPX1 electrotypes are described. Finally, we hypothesize an interaction between GPX1*2 and Hb beta*S allelic products occurring in the sickle cells infected by Plasmodium falciparum.

The selenium status of children with phenylketonuria: results of selenium supplementation.

The selenium status of children with phenylketonuria on a synthetic low phenylalanine diet was assessed. Correlation between blood selenium and red cell glutathione peroxidase was unsatisfactory (r = 0.65) due to the poor discrimination of red cell glutathione peroxidase with a low selenium diet. No symptoms of deficiency were observed. Supplementation with 50 micrograms per week of selenium as brewers yeast tablets over a period of 6 months significantly increased the blood selenium of the phenylketonuric children. Plasma Vitamin E levels were within normal limits. The supplementation effectively doubled their selenium intake to 15-17 micrograms per day, which is probably sufficient for this group with an adequate Vitamin E status, though considerably lower than the recommended minimum intake of 50 micrograms per day.

Proximal muscle weakness and selenium deficiency associated with long term parenteral nutrition

A 33-yr-old white female with short bowel syndrome secondary to trauma was maintained on home parenteral nutrition for 4 yr when her plasma, red cell, white cell, and platelet glutathione peroxidase (GSHPx) activities were found to be extremely low, as were her plasma and red cell selenium levels. During her first year on parenteral nutrition she noted the onset of an inability to rise from a squatting position, rapid tiring when stair climbing, and weakness when attempting to lift large or moderately heavy objects. Treatment with 400 µg/d of selenious acid intravenously was associated with a disappearance of her symptoms and an increase in proximal muscle strength within 6 wk. The plasma and red cell selenium levels, and the plasma and white cell GSHPx activities rose to normal levels within 6 wk. Red cell GSHPx activity returned to normal by 3 mo.

Effect of Selenium Supplementation on Selenium Balance in the Dependent Elderly

Although trace minerals are necessary constituents of enzymes, dietary requirements of these nutrients for the elderly are unknown. This study measured selenium balance in six dependent elderly men before and after five weeks daily administration of 200 micrograms organically-bound selenium; dietary selenium intake averaged 62.1 +/- 7 micrograms/day during both study periods. Selenium status was assessed not only chemically but also biologically as red cell and platelet glutathione peroxidase activities. Plasma selenium averaged 8.8 +/- 0.8 micrograms% (normal: 10 +/- 2 micrograms %) when intake derived from dietary sources alone and increased during medicinal supplementation to an average of 12.8 +/- 1.9 micrograms %. The rise in plasma selenium was not associated with an increase in red cell or platelet glutathione peroxidase activity. The effect of selenium supplementation on in vivo platelet aggregability was studied by measuring plasma levels of beta-thromboglobulin and platelet factor 4, two proteins secreted concomitant with aggregation. beta-thromboglobulin diminished 7.5 +/- 11.0 ng/ml and platelet factor 7.6 +/- 11.0 ng/ml during selenium supplementation despite no change in platelet glutathione peroxidase activity. These data support the concept that selenium nutritional status should be assessed not only by blood selenium content but also by selenium-dependent enzyme activity or selenium-dependent biologic effect.

Inactivation of red cell glutathione peroxidase by divicine and its relation to the hemolysis of favism

A significant inactivation of red blood cell glutathione peroxidase (25% less than the physiological value) was observed after exposure of intact erythrocytes to 2 mM divicine (an autoxidizable aminophenol from Vicia faba seeds) and 2 mM ascorbate for 3 h at 37°C. Addition of catalase and conversion of Hb to the carbomonoxy derivative resulted in protection against enzyme inactivation. Oxidation of Hb was a concurrent phenomenon, and augmented the inactivating effect. In hemolysates, much stronger effects were observed at shorter times (2 h); divicine was effective also without ascorbate, and the presence of reductants (ascorbate or glutathione or NADPH) enhanced its inactivating power. Of the other antioxidant enzymes, superoxide dismutase was unaffected under the same experimental conditions. Catalase was found to be much less sensitive to the inactivation; it was almost unaffected in experiments with intact erythrocytes and specifically protected by NADPH in experiments with hemolysates. This specific damage of glutathione peroxidase, apparently involving interaction of H 2O 2 and HbO 2, may be related to the pathogenesis of hemolysis in favism.

Selenium repletion and glutathione peroxidase— differential effects on plasma and red blood cell enzyme activity

We studied three children with chronic gastrointestinal disease who had been on intravenous hyperalimentation for periods of time ranging from 4 to 23 months. Each child was found to have low plasma and red blood cell glutathione peroxidase activity. This was associated, in the two children tested, with a marked deficiency of serum selenium. Their plasma glutathione peroxidase levels ranged between 4 and 24% of normal and their red blood cell levels ranged between 4 and 14% of normal. The intravenous alimentation was then supplemented with sodium selenite (240 micrograms Se/d). Within 4-5 weeks, the plasma glutathione peroxidase activity returned to normal. Red cell glutathione peroxidase activity remained essentially unchanged for 4-6 weeks, after which it increased over the following 3-4 months. Red cells were separated by density on a continuous Percoll-diatrizoate gradient. In normal individuals, the specific activity of glutathione peroxidase did not differ across the gradient despite a 2.5-fold difference in the specific activity of pyruvate kinase. When studied initially, glutathione peroxidase activity from the deficient patients did not change across the gradient. As the red cell enzyme activity increased with selenium repletion, the highest specific activity was initially found at the top of the gradient (youngest cells). After 3-4 months of supplementation, the specific activity became equal across the gradient. Thus, with selenium repletion, there is a rapid increase in plasma glutathione peroxidase activity, a 4-6 week lag prior to an increase in red cell enzyme activity, and the increase in red cell activity is due to newly synthesized red cells made in the presence of selenium.

Red cell glutathione peroxidase (GPX1) variation in Afro-Jamaican, Asiatic Indian, and Dutch populations. Is the GPX1*2 allele of "Thomas" variant an African marker?

A Cellogel procedure for screening the electrophoretic variants of the human red cell glutathione peroxidase ( GPX1 ) was described. Three hundred and ninety eight Dutch persons living in various parts of The Netherlands, 385 individuals born in various states of India, and 72 Jamaicans of African origin living in Birmingham, UK, were screened for GPX1 variants. The Dutch were monomorphic, while one Afro-Jamaican female and two males and one female of the 116 Punjabis were found to be variants indistinguishable from each other in their pattern of electrophoresis. The clear five banded pattern of the variant indicated that the subunit structure of the human red cell glutathione peroxidase is most probably a tetramer and suggested that the variant is the expression of a heterozygote due to alleles at an autosomal locus. The corresponding phenotype was designated tentatively as GPX1 2-1 and the alleles as GPX1 *1 and GPX1 *2 respectively. The variant 2-1 was found to be identical to the "Thomas" variant described by Beutler and West (1974). Thus so far, in addition to the Afro-Americans and Ashkenazi Jews (Beutler et al. 1974), the Punjabis of the Indian subcontinent (this report) were found to exhibit the GPX1 polymorphism due to the GPX1 *2 allele. The data discussed in this paper (which included unpublished observations on several African and non-African populations) suggest that the GPX1 *2 allele is originally an African variant and hint that the present day Punjabis of Indian subcontinent, like Ashkenazi Jews, are "predominantly of Mediterranean origin with some proportion of African ancestry" ( Mourant et al. 1976).

Hematologic and selenium status of low-birth-weight infants fed formulas with and without iron

Preterm infants with birth weights between 1,001 and 1,600 gm were randomly assigned at one week of age to three groups and fed a standard milk-based formula, the same formula with iron, or a soy-based formula with iron. Hematologic values and selenium status were then studied prospectively for five weeks. Rates of decline in hematocrit and hemoglobin did not differ significantly among the three groups and did not correlate with red cell selenium values or glutathione peroxidase activity. Attainment of vitamin E sufficiency was variable among the infants, with no significant intergroup differences. Plasma selenium concentrations did not change significantly, but plasma glutathione peroxidase activity declined consistently in all three groups. Under the conditions of this study, iron at a concentration of 12 mg/L of infant formula did not accelerate hemolysis; nor was there evidence of a direct association between selenium values and early anemia of prematurity.

Red cell glutathione peroxidase in various Jewish ethnic groups in Israel.

Red cell glutathione peroxidase (GSH-Px) activity has been measured in samples from seven Jewish population groups in Israel. No significant differences were found between the various communities. The mean GSH-Px activity was similar to that observed by Beutler and Matsumoto in Jewish samples from the USA and Israel. According to a genetic model proposed by the above investigators, the sample was subdivided into three phenotypes with low, intermediate and high activity, suggesting gene frequencies of 0.5072 and 0.4928 for the GSH-PxL and GSH-PxH alleles, respectively.

465 HEMATOLOGICAL AND BIOCHEMICAL CHANGES IN PREMATURE INFANTS ON 3 COMMERCIAL INFANT FORMULAS

Thirty healthy premature infants with birth weights between 1000g and 1600g were randomly assigned at 1 wk of age to 3 groups to determine the effect of 3 commercial infant formulas (Similac 20, Similac 20 with Iron, Iscmil - each containing 15 I.U. vit. E/liter) on various hematological, biochemical and growth parameters. During their hospital stay weekly determinations were made of hemoglobin (Hb); hematocrit (Hct); reticulocyte count; hydrogen peroxide hemolysis; red cell glutathione peroxidase (GSH-Px) and selenium (Se); plasma GSH-Px and Se; and serum Ca, P, alkaline phosphatase, protein, cholesterol and vit. E levels.Mean weekly rates of declines in Hb and in Hct, respectively, did not differ significantly in the 3 groups of infants. Among the infants with the highest rates of declines in Hct and Hb were some with persistently low serum vit. E levels; these were noted in all groups. Red cell and plasma GSH-Px and Se levels did not correlate with the rate of decline in Hb or Hct levels, nor was there a direct and constant correlation between hydrogen peroxide hemolysis and the rate of Hb decline. A decline in serum phosphorus levels was noted in all 3 groups, but was significantly greater (p<.01) in the Isomil group. Under the conditions of our study, iron at the concentration used in Similac with Iron (12 mg/L) did not appear to accelerate hemolysis. Individual variability in the hematological responses was noted irrespective of the formula used.

Glucose-6-phosphate dehydrogenase deficiency and red cell glutathione peroxidase

The activity of glutathione peroxidase (GSH Px), glucose-6-phosphate dehydrogenase (G-6-PD), hexokinase, and glutamic oxaloacetic transaminase (EGOT) was measured in 78 blood samples. GSH Px activity was not found to correlate with hexokinase or EGOT activity, indicating that it was not a strongly age-dependent enzyme. Although modest elevations of GSH Px activity were observed in the red cells of patients with a variety of hematologic disorders, the most consistent and striking increases in activity were observed in G-6-PD-deficient subjects.

Glucose-6-Phosphate Dehydrogenase Deficiency and Red Cell Glutathione Peroxidase

The activity of glutathione peroxidase (GSH Px), glucose-6-phosphate dehydrogenase (G-6-PD), hexokinase, and glutamic oxaloacetic transaminase (EGOT) was measured in 78 blood samples. GSH Px activity was not found to correlate with hexokinase or EGOT activity, indicating that it was not a strongly age-dependent enzyme. Although modest elevations of GSH Px activity were observed in the red cells of patients with a variety of hematologic disorders, the most consistent and striking increases in activity were observed in G-6-PD-deficient subjects.