Lower Glutathione Peroxidase Activity Research Articles

Long-Term Intake of High Doses of Vitamin C Down-regulates Anti-oxidant Enzymes in Human Erythrocytes

We located a group of healthy young males (aged 20~30) who had been taking a high dose (more than 5 g) of vitamin C daily for more than one year. We observed that this vitamin C group had plasma levels of vitamin C that were more than three times that of the control group. The control group had not taken any additional vitamin C except for that included in their diets. But the vitamin C group showed significantly lower amounts of Cu/ZnSOD, catalase and glutathione-s-transferase and lower activities of glutathione peroxidase and glutathione reductase in erythrocyte lysates than the control group. However, there was no difference in the plasma levels of lipid peroxides between the two groups. These results suggest that vitamin C offsets its own contribution to anti-oxidant activity by repressing the expression of anti-oxidant enzymes and also excludes the possibility that vitamin C acts as a pro-oxidant in vivo.

Effects of concentrated drinking water injection on glutathione and glutathione-dependent enzymes in liver of Cyprinus carpio L.

Two drinking water production plants located in North Italy, collecting water from the River Po (Plants 1 and 2) were chosen for this study. Water samples were collected before and after the disinfection process and at two points along the piping system. Water samples were concentrated by the solid-phase extraction system and injected intraperitoneally into specimens of Cyprinus carpio. The concentration of water samples was 3 l/equiv. In order to assess the effects of the water samples on carp liver, total glutathione and glutathione-dependent enzymes, such as glutathione S-transferase, glutathione peroxidase, glutathione reductase and glyoxalase I, were measured following this treatment for 6 days at two experimental times (3 and 6 days). Both water plant-treated carp showed a general increase of the enzymatic activities of glutathione S-transferase, and glutathione reductase which might be employed as potential biomarkers of oxidative stress induced by disinfected river water. Plant 1-treated carp showed higher glyoxalase I and glutathione levels and lower glutathione peroxidase activity. A depleted level of total glutathione and of glyoxalase I for specimens of water plant 2 (for both experimental times), without correlation with the distances in the pipeline, suggests that river plant water can also lead to potentially adverse effects on selected biochemical parameters in C. carpio.

Kinetics of hydrogen peroxide elimination by astrocytes and C6 glioma cells: Analysis based on a mathematical model

Oxidative stress is implicated in a variety of disorders including neurodegenerative diseases, and H 2O 2 is important in the generation of reactive oxygen and oxidative stress. In this study, we have examined the rate of extracellular H 2O 2 elimination and relevant enzyme activities in cultured astrocytes and C6 glioma cells and have analyzed the results based on a mathematical model. As compared with other types of cultured cells, astrocytes showed higher activity of glutathione peroxidase (GPx) but lower activities for GSH recycling. C6 cells showed relatively low GPx activity, and treatment of C6 cells with dibutyryl-cAMP, which induces astrocytic differentiation, increased catalase activity and H 2O 2 permeation rate but exerted little effect on other enzyme activities. A mathematical model [N. Makino, K. Sasaki, N. Hashida, Y. Sakakura, A metabolic model describing the H 2O 2 elimination by mammalian cells including H 2O 2 permeation through cytoplasmic and peroxisomal membranes: comparison with experimental data, Biochim. Biophys. Acta 1673 (2004) 149–159.], which includes relevant enzymes and H 2O 2 permeation through membranes, was found to be fitted well to the H 2O 2 concentration dependences of removal reaction with the permeation rate constants as variable parameters. As compared with PC12 cells as a culture model for neuron, H 2O 2 removal activity of astrocytes was considerably higher at physiological H 2O 2 concentrations. The details of the mathematical model are presented in Appendix.

Glial Dysfunction in Parkin Null Mice: Effects of Aging

Parkin mutations in humans produce parkinsonism whose pathogenesis is related to impaired protein degradation, increased free radicals, and abnormal neurotransmitter release. The role of glia in parkin deficiency is little known. We cultured midbrain glia from wild-type (WT) and parkin knock-out (PK-KO) mice. After 18-20 d in vitro, PK-KO glial cultures had less astrocytes, more microglia, reduced proliferation, and increased proapoptotic protein expression. PK-KO glia had greater levels of intracellular glutathione (GSH), increased mRNA expression of the GSH-synthesizing enzyme gamma-glutamylcysteine synthetase, and greater glutathione S-transferase and lower glutathione peroxidase activities than WT. The reverse happened in glia cultured in serum-free defined medium (EF12) or in old cultures. PK-KO glia was more susceptible than WT to transference to EF12 or neurotoxins (1-methyl-4-phenylpyridinium, blockers of GSH synthesis or catalase, inhibitors of extracellular signal-regulated kinase 1/2 and phosphatidylinositol 3 kinases), aging of the culture, or combination of these insults. PK-KO glia was less susceptible than WT to Fe2+ plus H2O2 and less responsive to protection by deferoxamine. Old WT glia increased the expression of heat shock protein 70, but PK-KO did not. Glia conditioned medium (GCM) from PK-KO was less neuroprotective and had lower levels of GSH than WT. GCM from WT increased the levels of dopamine markers in midbrain neuronal cultures transferred to EF12 more efficiently than GCM from PK-KO, and the difference was corrected by supplementation with GSH. PK-KO-GCM was a less powerful suppressor of apoptosis and microglia in neuronal cultures. Our data prove that abnormal glial function is critical in parkin mutations, and its role increases with aging.

Role of glutathione peroxidase in the ontogeny of hippocampal oxidative stress and kainate seizure sensitivity in the genetically epilepsy-prone rats

Oxidative stress may contribute to epileptogenicity in genetic models of epilepsy. To address this, we examined the enzymatic activity of cytosolic Cu/Zn superoxide dismutase (SOD-1), mitochondrial Mn superoxide dismutase (SOD-2), and glutathione peroxidase (GPx) in the developing hippocampus of genetically epilepsy-prone rats (GEPR-9s). We also measured changes in the GSH/GSSG ratio, lipid peroxidation, and protein oxidation at post-natal days (PD) 7, 30, and 90, respectively. Compared with control Sprague-Dawley (SD) rats, GEPR-9s showed similar SOD-1 and SOD-2 activity but lower GPx activity. Epilepsy-prone rats also showed lower GSH/GSSG ratios than controls, and more lipid peroxidation (as measured by malondialdehyde levels) and protein oxidation (as measured by carbonyl levels). Treatment with kainic acid (KA) resulted in more pronounced seizures, less GPx activity, and lower GSH/GSSG ratios in GEPR-9s than in controls, but KA did not significantly affect SOD-1 or SOD-2 activity, suggesting that GEPR-9s do not compensate for reduced GPx activity by increasing SOD. Moreover, KA treatment resulted in significantly a lower GSH/GSSG ratio and GPx-like immunoreactivity and higher malondialdehyde and carbonyl levels in GEPR-9s than in controls. These findings were more evident in GEPR-9s at PD 90 than at PD 30, indicating that oxidative stress is age-dependent. Double-labeling immunocytochemical analysis demonstrated co-localization of GPx-immunoreactive glia-like cells and reactive astrocytes, as labeled by glial fibrillary acidic protein (GFAP). This suggests that mobilization of astroglial cells for synthesis of GPx protein is a response to KA insult, intended to decrease the neurotoxicity induced by peroxides. These responses were more pronounced in control SD rats than in GEPR-9s. Our results suggest that impairment of the GPx (including glutathione)-mediated antioxidant system contributed to epileptogenesis in GEPR-9s.

Oxidative stress in patients with COPD and pulmonary hypertension

Oxidative stress plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Oxidant/antioxidant imbalance has also been reported in various forms of pulmonary hypertension. The present study aimed to assess systemic oxidative stress, as reflected by serum malondialdehyde (MDA) concentrations and activities of antioxidant enzymes in erythrocytes [glutathione peroxidase (GPX), superoxide dismutase (SOD) and catalase (CAT)] in patients with and without pulmonary hypertension secondary to COPD. Seventy-five patients (58 male) with COPD (mean age 65.1 +/- 1.2 years; mean smoking history 35.6 +/- 3.8 pack-years) were studied. Twenty-one healthy non-smokers served as a control group. Pulmonary function was evaluated with body plethysmography; mean and systolic pulmonary artery pressures (Ppa) were assessed with Doppler echocardiography. Serum concentrations of MDA and activities of GPX, SOD and CAT in washed red blood cells were measured using spectrophotometry. Pulmonary hypertension was present in 28 patients with COPD (systolic Ppa: 46.4 +/- 2.3 mmHg; mean Ppa: 26.0 +/- 1.9 mmHg) and absent in 47 (systolic Ppa: 22.9 +/- 0.8 mmHg; mean Ppa: 13.4 +/- 0.6 mmHg). Compared with the healthy control group, all the patients (with or without pulmonary hypertension) had higher serum MDA concentrations (1.5 +/- 0.1 versus 2.3 +/- 0.1 versus 2.3 +/- 0.1 nmol/mL, ANOVA, P < 0.001) and lower erythrocyte GPX activity (51.3 +/- 3.2 versus 42.2 +/- 2.0 versus 41.3 +/- 2.5 U/g Hb, P = 0.029), whereas SOD (1121.1 +/- 29.0 versus 1032.6 +/- 21.8 versus 1032.7 +/- 36.2 U/g Hb, P = 0.063) and CAT activities (4.9 +/- 0.2 versus 4.6 +/- 0.1 versus 4.7 +/- 0.2 U/g Hb; P= 0.454) were similar. No differences were observed in serum MDA concentrations or activities of GPX, SOD and CAT in erythrocytes between COPD patients with and without pulmonary hypertension. The study demonstrates the presence of oxidative/antioxidative imbalance in the systemic circulation in patients with COPD: compared with healthy subjects, COPD patients had higher serum MDA concentrations and lower GPX activity in erythrocytes. The magnitudes of the increase in MDA and reduction in GPX activity were similar in COPD patients with pulmonary hypertension and in those with normal pulmonary artery pressures.

Nutritional myodegeneration as a cause of dysphagia in adult horses: three case reports

Three cases of nutritional myodegeneration caused by selenium deficiency in adult horses are described. Difficulty in eating and drinking was a common clinical sign in all horses. Blood biochemistry revealed a marked elevation of muscle enzymes and low glutathione peroxidase activity or low selenium concentration in whole blood in all cases. The treatment with sodium selenite and vitamin E was instituted in all horses. Two of them were euthanized because of continuing muscle injuries, one patient was cured. The post-mortem examination of euthanized horses revealed pale muscles that were distributed with bilateral symmetry on hind and thoracic limbs, diaphragm, tongue, masticatory and intercostal muscles and the myocardium. Histopathology revealed the areas of degeneration and necrosis. Large groups of regenerating fibres and pronounced lymphoplasmocytic reaction among the groups of intact fibres were also present. The clinical outcome of the disease is probably influenced by timely diagnosis and treatment.

Low glutathione peroxidase in rd1 mouse retina increases oxidative stress and proteases

Malondialdehyde, reduced glutathione, glutathione peroxidase, glutathione reductase and cysteine protease cathepsins at postnatal (PN) days 2, 7, 14, 21 and 28 in controls (wt) and the retinal degeneration 1 (rd1) mouse model for retinitis pigmentosa retinas were measured to determine oxidative stress. In PN28 wt and PN2 rd1 retinas, elevated malondialdehyde and low glutathione peroxidase activity indicate higher oxidative load, despite higher reduced glutathione in PN2 rd1 retinas. This is due to physiological exposure to light and retinal vascular/neural restructuring, respectively. Compared with wt retinas, relatively high malondialdehyde at PN2 and cathepsin levels at PN14, 21 and 28 in rd1 retinas indicate that cells of the residual inner retina also contribute to the oxidative stress and retinal degeneration.

High superoxide dismutase and low glutathione peroxidase activities in red blood cells predict susceptibility of lung cancer patients to radiation pneumonitis

Radiation pneumonitis is an unpredictable complication of radiotherapy for lung cancer and a condition which can cause significant morbidity. The ability to identify patients at a high risk of developing pneumonitis is critical, since it will enable the individualization of the treatment plan. Because the cytotoxic effect of radiation is propagated through reactive oxygen species (ROS) and ROS-driven oxidative stress, the role of antioxidant defense systems in radiation pneumonitis was investigated. Using the pneumonitis-sensitive C3H/HeN mice as a model, we demonstrated that the antioxidant response of the lung correlated well with that of red blood cells (RBC). We then proceeded to test whether differences of RBC antioxidant response would predict the pneumonitis development in patients. Superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase (CAT) activities and glutathione in RBC were measured at baseline and then weekly for 6 weeks of treatment in 15 eligible patients receiving concurrent chemo-radiotherapy for unresectable stage III NSCLC. Striking differences were found in the antioxidant activities of RBC with respect to the pneumonitis development. Those who developed pneumonitis showed higher SOD and lower GPX activities at baseline compared to those who did not (3.7 vs 6.8 units/mg for median SOD, 16.5 vs 10.7 nmol/min/mg for median GPX). The functional imbalance of SOD and GPX was displayed consistently throughout the treatment period. The sensitivity and specificity of pneumonitis prediction were further increased when the GPX/SOD ratio was analyzed (pretreatment P = 0.0046). Our results provide a strong rationale to monitor SOD and GPX activities of RBC to identify patients who are at risk of developing pneumonitis, and to implement a strategy of increasing the GPX/SOD ratio in order to lower the risk.

2458: High Superoxide Dismutase (SOD) and Low Glutathione Peroxidase (GPX) Activities in Red Blood Cells (RBCs) Predict Susceptibility of Lung Cancer Patients to Radiation Pneumonitis

2458: High Superoxide Dismutase (SOD) and Low Glutathione Peroxidase (GPX) Activities in Red Blood Cells (RBCs) Predict Susceptibility of Lung Cancer Patients to Radiation Pneumonitis

Closely related colon cancer cell lines display different sensitivity to polyunsaturated fatty acids, accumulate different lipid classes and downregulate sterol regulatory element‐binding protein 1

N-6 polyunsaturated fatty acids (PUFAs) may be associated with increased risk of colon cancer, whereas n-3 PUFAs may have a protective effect. We examined the effects of docosahexaenoic acid (DHA), eicosapentaenoic acid and arachidonic acid on the colon carcinoma cell lines SW480 derived from a primary tumour, and SW620 derived from a metastasis of the same tumour. DHA had the strongest growth-inhibitory effect on both cell lines. SW620 was relatively more growth-inhibited than SW480, but SW620 also had the highest growth rate in the absence of PUFAs. Flow cytometry revealed an increase in the fraction of cells in the G2/M phase of the cell cycle, particularly for SW620 cells. Growth inhibition was apparently not caused by increased lipid peroxidation, reduced glutathione or low activity of glutathione peroxidase. Transmission electron microscopy revealed formation of cytoplasmic lipid droplets after DHA treatment. In SW620 cells an eightfold increase in total cholesteryl esters and a 190-fold increase in DHA-containing cholesteryl esters were observed after DHA treatment. In contrast, SW480 cells accumulated DHA-enriched triglycerides. Arachidonic acid accumulated in a similar manner, whereas the nontoxic oleic acid was mainly incorporated in triglycerides in both cell lines. Interestingly, nuclear sterol regulatory element-binding protein 1 (nSREBP1), recently associated with cell growth regulation, was downregulated after DHA treatment in both cell lines. Our results demonstrate cell-specific mechanisms for the processing and storage of cytotoxic PUFAs in closely related cell lines, and suggest downregulation of nSREBP1 as a possible contributor to the growth inhibitory effect of DHA.

Practicalities of selenium supplementation in critically ill patients

To review the reason for and clinical effects of selenium supplementation in critically ill patients. Selenium-dependent enzymes and selenoprotein P regulate immune and endothelial cell function. Obviously not the anorganic compounds of selenium but the activity of selenium-dependent enzymes is the most important factor modulating the immune system and the clinical outcome of patients. Despite low selenium levels in severely ill patients and low glutathione peroxidase activity associated with the extent of multiorgan dysfunction, only a few trials have investigated the effect of selenium supplementation on clinical outcome. A metaanalysis did not reveal a statistically significant survival rate with selenium supplementation, but suggested a dose-dependent trend. The recently completed multicentre trial on high-dose selenium supplementation in septic patients also did not reveal a significant overall reduction in mortality. The available evidence suggests that selenoproteins play an important role in the immunomodulation of critically ill patients and a sodium selenite supplementation upregulates these selenoenzymes. The intervention trials with sodium selenite performed to date are small and therefore only a tendency in reduction of morbidity and mortality could be demonstrated. Larger trials are necessary to show the supposed benefits and risks of selenite supplementation in critically ill patients.

Oxidative stress and adhesion molecules in children with type 1 diabetes mellitus: a possible link

To examine whether oxidative stress parameters were correlated with adhesion molecules derived from endothelial/platelet activation in a group of juveniles with type 1 diabetes mellitus (T1DM). Indicative parameters of patient oxidant/antioxidant capacity were measured and associated with P-selectin and tetranectin (TN), markers of endothelial/platelet activation, in the plasma of 45 diabetic children and adolescents and 20 healthy age-matched subjects (HS). Significantly, higher nitrate/nitrite (NOx) and lipid hydroperoxide (LPO) levels (p=0.049 and p=0.0011, respectively), lower glutathione peroxidase activity (GPx; p=0.038), and elevated TN and P-selectin plasma levels (p=0.0046 and p=0.042, respectively) were found in T1DM children compared with HS. Well-controlled T1DM children (HbA1c <or= 7%) showed significantly lower GPx (p=0.0259), higher NOx and LPO (p=0.01093 and p=0.0092, respectively) compared with HS, while poorly controlled patients (HbA1c >7%) showed significantly higher TN, sP-selectin and LPO (p=0.0064, p=0.0234 and p=0.0121, respectively), a tendency to higher NOx (p=0.063) compared with HS and only TN higher (p=0.0123) compared with well-controlled patients. Patients with shorter diabetes duration (<or=3 yr) showed significantly higher LPO and TN (p=0.034 and 0.017, respectively), a tendency to higher NOx and lower GPx and higher P-selectin, while those with longer duration (>3 yr) differed significantly in all the examined parameters (TN, p=0.0015; GPx, p=0.0420; NOx, p=0.0196; LPO, p=0.0054; sP-selectin, p=0.0187) compared with HS. Decreased antioxidative protection from simultaneous LPO and NOx overproduction is evident in T1DM juveniles with a parallel endothelial/platelet activation even in the first years of the disease, being more pronounced later in diabetes progression, contributing to the vascular complications of the disease.

Possible involvement of selenium inStaphylococcus aureusinhibition in cow's whey

Previous investigations have shown that selenium supplementation inhibits growth of mastitis pathogens in cow's milk. The present study was performed to clarify the role of selenium in defence mechanisms of mammary gland. We have examined the effects of selenium supplementation on Staphylococcus aureus growth inhibiting activity in whey. Six selenium-supplemented and six non-supplemented Estonian dairy cows were used for this study. Selenium-supplemented cows received 4 mg organic selenium in the form of selenium yeast in their daily diet for 8-week period. Cows from non-supplemented group received the same amount of yeast free of selenium in their diet. All cows had initially low blood glutathione peroxidase (GPx) activity (<or=1.02 microkat/g Hb). During the 8-week experiment these cows had low somatic cell count (<300,000 cells/ml) and negative bacteriological findings in their quarter milk samples. Bacterial growth inhibitory activity in specific whey fractions was clearly evident in 3 out of 6 cows supplemented with selenium. The inhibitory effect was more profound if the cow's blood GPx activity exceeded 4 microkat/g Hb, whereas in non-supplemented cows the inhibition of S. aureus growth was not observed. This study confirms the presence of selenium-dependent antibacterial activity in cow's milk.

A diet rich in phosphatidylethanolamine increases plasma homocysteine in mink: a comparison with a soyabean oil diet

The effects of high dietary levels of phosphatidylethanolamine (PE) on plasma concentrations of homocysteine (tHcy) have not previously been studied. Eighteen mink (Mustela vison) studied were fed one of three diets during a 25 d period in a parallel-group design. The compared diets had 0, 17 and 67 % extracted lipids from natural gas-utilising bacteria (LNGB), which were rich in PE. The group with 0 % LNGB was fed a diet of 100 % soyabean oil (SB diet). Phospholipids are the main lipid components in LNGB and Methylococcus capsulatus is the main bacteria (90 %). The fasting plasma concentration of tHcy was significantly higher when the mink consumed the diet with 67 % LNGB than when they consumed the SB diet (P=0.039). A significantly lower glutathione peroxidase activity was observed in mink consuming the 17 % LNGB diet or the 67 % LNGB diet than was observed in mink fed the SB diet. The lack of significant differences in the level of plasma PE due to the diets indicates that most of the PE from the 67 % LNGB diet was converted to phosphatidylcholine (PC) in the liver. It has previously been hypothesised that phosphatidylethanolamine N-methyltransferase is an important source of tHcy. The present results indicate that plasma tHcy is at least partly regulated by phospholipid methylation from PE to PC. This methylation reaction is a regulator of physiological importance.

Free radical injury and antioxidant status in patients with benign prostate hyperplasia and prostate cancer

Reactive oxygen species and other free radicals are known to be the mediators of phenotypic and genotypic changes that lead from mutation to neoplasia. There are some primary antioxidants such as glutathione peroxidase (GPx), glutathione S-transferases (GSTs) and reduced glutathione, which protect against callular and molecular damage caused by the reactive oxygen metabolites (ROMs). The present study was conducted to determine the level of malondialdehyde (MDA), as an index of lipid peroxidation, along with the GPx, GSTs activities and level of reduced glutathione in 45 prostate cancer (PC) patients, 55 benign prostate hyperplasia (BPH) patients as compared to the controls. Significant higher levels of MDA and GSTs activities in the serum, (P<0.005) and significant lower levels of reduced GSH concentration and GPx activity in blood haemolysates (P<0.05) of PC and BPH patients were observed as compared to the controls. The relatively higher GSTs activity and low level of reduced GSH may be due to the response of increased reactive oxygen metabolites production in the blood. The higher MDA and lower GPx activities may be inadequate to detoxify high levels of H(2)O(2) into H(2)O leading to the formation of the(*)OH radical followed by MDA. This result hypothesizes that oxidant-antioxidant imbalance may be one of the major factor responsible for the development of prostate cancer and benign prostate hyperplasia.

Role of oxidative stress in ethanol induced germ cell apoptosis - An experimental study in rats.

The study was undertaken to evaluate the possible involvement of oxidative stress in the pathogenesis of ethanol induced testicular atrophy in rats. Adult male rats were orally administered ethanol at a dose of 1.6 g/kg body weight/day for four weeks. Twenty-four hours after the last treatment the rats were sacrificed using anesthetic ether. Testes were removed and weighed. Apoptosis was studied by using the Feulgen reaction on 5 μ thin paraffin sections of testis. Testicular homogenate was prepared and centrifuged. The supernatant was used for the estimation of extent of lipid peroxidation and antioxidant defense status. There was significant reduction in body weight: and in testicular weight and diameter in ethanol treated rats. Extent of germ cell apoptosis was significantly high in ethanol treated rats. Ethanol treated rats showed significantly high tissue TBARS level and glutathione S-transferase activity; and low tissue ascorbic acid, reduced glutathione, superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase activities. Chronic ethanol administration resulted in high oxidative stress in the testes either due to increased extent of lipid peroxidation or due to decreased antioxidant defenses, and thereby induces germ cell apoptosis leading to testicular atrophy.

Race-Specific Differences in Antioxidant Enzyme Activity in Patients With Type 2 Diabetes

Lipid hydroperoxide, a marker of oxidative stress, is linked to the development of nephropathy and is reportedly higher in patients of African origin compared with Caucasians. This may be relevant to race-specific differences in susceptibility to nephropathy. We investigated whether alterations in antioxidant enzyme activity could account for this biochemical phenotype and examined the relationship with conventional markers of renal disease. Two hundred seventeen individuals were studied. Patients with type 2 diabetes (n = 75) of African and Caucasian origin were matched by sex and racial origin with healthy control subjects (n = 142). Plasma total superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity were spectrophotometrically measured, and total cholesterol and triglycerides were measured by enzymatic methods. SOD activity was higher and GPx activity lower in patients with diabetes than in healthy control subjects (573 +/- 515 vs. 267 +/- 70 units/l, P < 0.001 and 150 +/- 93 vs. 178 +/- 90 units/l, P = 0.019, respectively). Patients of African origin with diabetes had lower GPx and higher SOD activity compared with Caucasian patients (126 +/- 82 vs. 172 +/- 97 units/l, P = 0.03 and 722 +/- 590 vs. 445 +/- 408 units/l, P = 0.002, respectively). Patients of African origin with normal urinary albumin excretion had significantly higher plasma creatinine concentrations (100.7 +/- 14.2 vs. 88.1 +/- 14.9 micromol/l, P = 0.007) and lower GPx activity (99.0 +/- 72.4 vs. 173.7 +/- 107.4 units/l, P = 0.02) compared with those of Caucasian origin. African origin was an independent predictor of elevated SOD (P = 0.007) and reduced GPx activity (P = 0.02) in regression analysis. SOD and GPx enzyme activities vary according to race and could account for differences in lipid hydroperoxide. In patients of African origin, susceptibility to renal disease may be associated with lowered GPx activity.

Blood Lipid Peroxides and Muscle Damage Increased following Intensive Resistance Training of Female Weightlifters

The aim of this study was to examine changes in muscle cell injury and antioxidant capacity of weightlifters following a 1-week intensive resistance-training regimen. Thirty-six female subjects participated in this study, and their ages ranged from 18 to 25 years. The sample group included 19 elite weightlifters with more than 3 years of weightlifting training experience, while the control group comprised 17 non-athletic individuals. Compared with non-athletes, weightlifters had significantly lower glutathione peroxidase activity and plasma vitamin C concentrations. Weightlifters also had significantly higher malondialdehyde + 4-hydroxy 2-(E)-nonenal (MDA+4-HNE) and thiobarbituric acid-reactive substance (TBARS) levels and creatine kinase (CK) activity. For weightlifters, the plasma vitamin E level and the activity of superoxide dismutase (SOD) decreased, and CK activity increased significantly (P < 0.05) after a 1-week intensive resistance-training regimen. Both the TBARS levels and CK activity returned to values of pre-intensive training after a 2-day rest. The MDA+4-HNE level strongly correlated with CK activity in weightlifters (P < 0.05). In conclusion, both long-term exercise training and 1 week of intensive resistance training resulted in increased oxidative stress and cell injury in female weightlifters. Furthermore, proper rest after intensive training was found to be important for recovery.

Antioxidant defences in cybrids harboring mtDNA mutations associated with Leber's hereditary optic neuropathy

Oxidative stress and imbalance between free radical generation and detoxification may play a pivotal role in the pathogenesis of Leber's hereditary optic neuropathy (LHON). Mitochondria, carrying the homoplasmic 11778/ND4, 3460/ND1 and 14484/ND6 mtDNA point mutations associated with LHON, were used to generate osteosarcoma-derived cybrids. Enhanced mitochondrial production of reactive oxygen species has recently been demonstrated in these cybrids [Beretta S, Mattavelli L, Sala G, Tremolizzo L, Schapira AHV, Martinuzzi A, Carelli V & Ferrarese C (2004) Brain 127, 2183-2192]. The aim of this study was to characterize the antioxidant defences of these LHON-affected cells. The activities of glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutases (SOD) and catalase, and the amounts of glutathione (GSH) and oxidized glutathione (GSSG) were measured in cybrids cultured both in glucose-rich medium and galactose-rich medium. The latter is known to cause oxidative stress and to trigger apoptotic death in these cells. In spite of reduced SOD activities in all LHON cybrids, and of low GPx and GR activities in cells with the most severe 3460/ND1 and 11778/ND4 mutations, GSH and GSSG content were not significantly modified in LHON cybrids cultured in glucose medium. In contrast, in galactose, GSSG concentrations increased significantly in all cells, indicating severe oxidative stress, whereas GR and MnSOD activities further decreased in all LHON cybrids. These data suggest that, in cells carrying LHON mutations, there is a decrease in antioxidant defences, which is especially evident in cells with mutations associated with the most severe clinical phenotype. This is magnified by stressful conditions such as exposure to galactose.