Detoxification Of Superoxide Radicals Research Articles

Circulating Superoxide Dismutase Concentrations in Obstructive Sleep Apnoea (OSA): A Systematic Review and Meta-Analysis.

Obstructive Sleep Apnoea (OSA) is characterized by a pro-oxidant state that results from the recurrent hypoxia-reoxygenation cycles. Superoxide dismutase (SOD), a key antioxidant enzyme involved in the detoxification of superoxide radicals, could represent a reliable marker to monitor the antioxidant defences in OSA. In order to capture and critically appraise the available evidence, we performed a systematic review and meta-analysis of studies reporting SOD concentrations in OSA patients and non-OSA controls in the electronic databases Pubmed, Web of Science, Scopus and Google Scholar. In total, 13 studies in 847 OSA patients and 438 non-OSA controls were included in the meta-analysis. Blood SOD concentrations were significantly lower in OSA patients (SMD = 0.87, p < 0.001). By contrast, serum/plasma SOD concentrations were not significantly different between the two groups. Although extreme between-study heterogeneity was observed, the SMD was not substantially modified when individual studies were sequentially removed. In conclusion, we observed that whole blood, but not serum/plasma, SOD concentrations were significantly lower in OSA patients compared with controls. Our meta-analysis suggests an impaired antioxidant defence in OSA that is more robustly assessed in the corpuscular biological matrix and provides useful background information for further studies investigating the association between SOD changes and clinical status in OSA.

Erythrocyte Superoxide Dismutase Activity is Higher in Younger Than in Older Schizophrenics

Introduction Superoxide dismutase (SOD) is the critical enzyme in the detoxification of superoxide radicals because those are the first species produced in the majority of biological free radical producing reactions. Inconsistent data are present about SOD activity in patients with schizophrenia. Aims To compare erythrocyte SOD activity in schizophrenic patients who were randomly selected, and separately in the subgroup of patients younger than 34 years. Methods This study included 68 consecutive patients with schizophrenia (29 males and 39 females) mean age 32.7±9.4 years. The results of whole group were tested with 59 healthy controls and with the subgroup of patients younger than 34 years. SOD activity was measured in erythrocyte hemolysates by Ransod commercially available test. Results When we tested the whole patient group SOD activity was not significantly different between the healthy controls and schizophrenics. In the subgroup of patients younger than 34 years SOD levels were significantly higher (1525±279 U/gHb, p Conclusion Our results showed that SOD activity is significantly increased in the early phase of the disease, and then declined to control values.

Association of altered CuZn superoxide dismutase and cognitive impairment in schizophrenia patients with tardive dyskinesia

Free radical-mediated abnormalities may contribute to the development of tardive dyskinesia (TD) and specific aspects of schizophrenia symptomatology such as cognitive deficits. Superoxide dismutase (SOD), a critical enzyme in the detoxification of superoxide radicals, was found to be abnormal in TD. While most of previous studies focused on the manganese isoform located in mitochondria, this study investigated the activities of isoform CuZnSOD present in the plasma. We recruited 113 male chronic patients with TD (n = 43) and without TD (n = 70) meeting DSM-IV criteria for schizophrenia, and 84 male control subjects. We examined the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), CuZnSOD activity for both the patient and control groups along with total antioxidant status (TAS) and malondialdehyde (MDA) levels in a subset of the cohort. Positive and Negative Symptom Scale (PANSS) and the Abnormal Involuntary Movement Scale (AIMS) were assessed in the patient group. Our results showed lower CuZnSOD activity and TAS levels, but higher MDA levels in patients with TD than those without TD (all p < 0.05). Patients with TD had lower RBANS subscales of Visuospatial/Constructional (p < 0.05) and attention (p < 0.01) than those without TD. Multiple regression analysis showed that in either TD or non-TD group, CuZnSOD was an independent contributor to the attention index of RBANS (both p < 0.05). These results implicated that TD patients suffered greater oxidative stress and cognitive dysfunction than non-TD patients. Oxidative stress could contribute to both TD development and cognitive impairment.

Overexpression of Manganese Superoxide Dismutase Does Not Increase Clonogenic Cell Survival Despite Effect on Apoptosis in Irradiated Lymphoblastoid Cells

Gene therapy-mediated overexpression of superoxide dismutases (SOD) appears to be a promising strategy for modulating radiosensitivity based on detoxification of superoxide radicals and suppression of apoptosis. Using recombinant lentiviral-based vectors, the effects of SOD overexpression on both were tested in human lymphoblastoid cells (TK6) that are sensitive to radiation-induced apoptosis. TK6 cells were transduced with vectors containing CuZnSOD, MnSOD or inverted MnSOD (MSODi) cDNA. Gene transfer efficiency, SOD activity, superoxide-radical resistance, apoptosis and clonogenic survival were determined. A six- to eightfold increase in SOD activity was observed after transduction, rendering MnSOD-overexpressing TK6 cells significantly more resistant to paraquat-induced superoxide radical production than controls. Although significant differences in sensitivity to apoptosis were observed for MnSOD, no differences in clonogenic survival after irradiation were detected between any groups. Our data show that efficient cellular SOD overexpression, an increased superoxide radical detoxifying ability and, for MnSOD, decreased apoptosis did not result in increased clonogenic survival after irradiation. This strengthens the hypothesis of differences in the radiation-modulating effects of SOD on normal and malignant cells (protective and nonprotective, respectively), thereby showing its potential to increase the therapeutic index in future clinical SOD-based radioprotection approaches.

Elevated plasma superoxide dismutase in first-episode and drug naive patients with schizophrenia: Inverse association with positive symptoms

Excessive free radical production or oxidative stress may be involved in the pathophysiology of schizophrenia as evidenced by increased superoxide dismutase (SOD) activities, a critical enzyme in the detoxification of superoxide radicals. This study compared plasma SOD activities in 78 never-medicated first-episode and 100 medicated chronic schizophrenia patients to 100 healthy control subjects and correlated these SOD activities with the Positive and Negative Syndrome Scale (PANSS) among the schizophrenic patients. We found that both first-episode and chronic patients had significantly increased plasma SOD activities compared to controls, and that chronic schizophrenic patients on antipsychotic medication had significantly higher SOD activities than first episode schizophrenic patients. Plasma SOD activities were also negatively correlated with positive symptoms of schizophrenia, but only in first-episode patients. Thus, oxidative stress appears to be greater in first episode schizophrenic patients with fewer positive symptoms and may become greater as schizophrenia becomes more chronic, although we cannot exclude the possibility that chronic antipsychotic treatment may increase SOD activities and presumed oxidative stress in schizophrenia.

Direct Magnetic Resonance Evidence for Peroxymonocarbonate Involvement in the Cu,Zn-Superoxide Dismutase Peroxidase Catalytic Cycle

Cu,Zn-superoxide dismutase (SOD1) is a copper- and zinc-dependent enzyme. The main function of SOD1 is believed to be the scavenging and detoxification of superoxide radicals. Nevertheless, the last 30 years have seen a rapid accumulation of evidence indicating that SOD1 may also act as a peroxidase, an alternative function that was implicated in the onset and progression of familial amyotrophic lateral sclerosis. Although SOD1 peroxidase activity and its dependence on carbon dioxide have been well described, the molecular basis of the SOD1 peroxidase cycle remains obscure, because none of the proposed catalytic intermediates have so far been identified. In view of recent observations, we hypothesized that the SOD1 peroxidase cycle relies on two steps: 1) reduction of SOD-Cu(II) by hydrogen peroxide followed by 2) oxidation of SOD-Cu(I) by peroxymonocarbonate, the product of the spontaneous reaction of bicarbonate with hydrogen peroxide, to produce SOD-Cu(II) and carbonate radical anion. This hypothesis has been investigated through electron paramagnetic resonance and nuclear magnetic resonance to provide direct evidence for a peroxycarbonate-driven, SOD1-catalyzed carbonate radical production. The results gathered herein indicate that peroxymonocarbonate (HOOCO(2)(-)) is a key intermediate in the SOD1 peroxidase cycle and identify this species as the precursor of carbonate radical anions.

HMA1, a New Cu-ATPase of the Chloro plast Envelope, Is Essential for Growth under Adverse Light Conditions

Although ions play important roles in the cell and chloroplast metabolism, little is known about ion transport across the chloroplast envelope. Using a proteomic approach specifically targeted to the Arabidopsis chloroplast envelope, we have identified HMA1, which belongs to the metal-transporting P1B-type ATPases family. HMA1 is mainly expressed in green tissues, and we validated its chloroplast envelope localization. Yeast expression experiments demonstrated that HMA1 is involved in copper homeostasis and that deletion of its N-terminal His-domain partially affects the metal transport. Characterization of hma1 Arabidopsis mutants revealed a lower chloroplast copper content and a diminution of the total chloroplast superoxide dismutase activity. No effect was observed on the plastocyanin content in these lines. The hma1 insertional mutants grew like WT plants in standard condition but presented a photosensitivity phenotype under high light. Finally, direct biochemical ATPase assays performed on purified chloroplast envelope membranes showed that the ATPase activity of HMA1 is specifically stimulated by copper. Our results demonstrate that HMA1 offers an additional way to the previously characterized chloroplast envelope Cu-ATPase PAA1 to import copper in the chloroplast.

Blood superoxide dismutase level in schizophrenic patients with tardive dyskinesia: association with dyskinetic movements

Free radicals may be involved in the pathogenesis of tardive dyskinesia (TD). Superoxide dismutase (SOD), a critical enzyme in the detoxification of superoxide radicals, was found to be abnormal in TD. To examine the blood SOD levels in schizophrenic patients with and without TD, and the relationships between SOD levels and tardive dyskinesia symptoms in TD patients, 45 physically healthy patients with TD who met DSM-III-R criteria for schizophrenia were compared with 45 schizophrenic patients without TD, as well as with 50 age-, sex- and smoking-matched normal controls. The severity of TD was assessed using the abnormal involuntary movement scale (AIMS). The psychopathology of patients were assessed by the Positive and Negative Syndrome Scale (PANSS). Blood SOD levels were measured by radioimmunometric assay (RIA). The results showed that the patients with TD had lower concentrations of blood SOD than those without TD, but had higher blood SOD levels than the normal controls. In the patients with TD, AIMS total score was inversely correlated with SOD levels. Our data support the view that free radicals may be involved in the pathophysiology of TD. There may exist a relationship between the free radical metabolism and the severity of dyskinesia of TD patients.

Association between manganese superoxide dismutase (MnSOD) gene polymorphism and breast cancer risk.

Superoxide dismutases play a key role in the detoxification of superoxide radicals and thus protect cells from damage induced by free radicals. Within mitochondria manganese superoxide dismutase (MnSOD) provides a major defence against oxidative damage by reactive oxygen species. Polymorphism in the mitochondrial targeting sequence of MnSOD has recently been associated with risk of breast cancer. We examined this in a study population consisting of 483 breast cancer cases and 482 controls, all of Finnish Caucasian origin. Odds ratios (OR) and 95% confidence intervals (95% CIs) were estimated by unconditional logistic regression. MnSOD genotypes containing the variant A allele were found to be associated with a 1.5-fold (95% CI 1.1-2.0) increased risk of breast cancer compared with those with the homozygous wild-type genotype (MnSOD VV). This finding supports the proposal that MnSOD genotypes may modify individual breast cancer risk.

Reduced plasma ascorbic acid and red cell glutathione contents in sickle cell disease—A preliminary report

Glutathione and ascorbic acid in erythrocytes are suggested to be essential in the detoxification of superoxide radicals and hydrogen peroxide formed during red cell metabolism. In sickle cell patients who are more prone to haemolysis have greater propensity for the formation of superoxide radical and hydrogen peroxide. In the present study conducted on sickle cell patients provide evidence for the presence of reduced levels of both ascorbic acid and glutathione in the red cells. This may seem to suggest that vitamin C supplementation may help such patients who are prone to haemolysis.

Effects of Superoxide Dismutase and Allopurinol on the Survival of Acute Island Skin Flaps

We have demonstrated previously that oxygen-derived free radicals are important mediators of tissue injury following ischemia (total venous occlusion) and reperfusion in small (3 cm X 6 cm) island skin flaps in rats. In this study, we evaluated extension of this concept to regional ischemia in large (8 cm X 8 cm) acute island skin flaps which were constructed to exceed their sole blood supply via unilateral inferior epigastric vessels. Under normal (control) circumstances, a significant portion of the flap would undergo necrosis at the periphery, mimicking the corresponding clinical situation. Blocking the generation of superoxide radicals from xanthine oxidase with a single dose of allopurinol prior to flap elevation significantly improved the area of flap viability from 34 +/- 12% to 57 +/- 6% (p less than 0.01) in the random portion of the flap, contralateral to the source of blood supply. Similarly, the detoxification of superoxide radicals with a single dose of superoxide dismutase improved viability from 41 +/- 6% to 58 +/- 7% (p less than 0.01). Similar results were obtained when either of these agents were administered 60 minutes after flap elevation. These findings suggest that oxygen-derived free radicals play an important role in the development of tissue necrosis in the critical transition zone between well-vascularized and devascularized skin.