Imbalance In Antioxidant Enzymes Research Articles

Exploring the Anti-Cancer Properties of Pomegranate Peel Aqueous Extract

The objective of this work is to evaluate the influence of pomegranate peel extract (PPE) in the behavior of breast cell lines (epithelial and tumor type) and related oxidative metabolism. Fruit-based functional foods have been the target of increasing scientific research for their physiological and pathophysiological properties. Pomegranate (Punica granatum) is a suitable example with both prophylactic and medicinal effects. MCF-7 cell line from tumor breast carcinoma, and MCF-10A cell line from normal epithelial mammary gland were used and subjected to different concentrations of PPE, ranging from 1 to 5 mM of gallic acid equivalents (GAE). Viability, proliferation, mobility, and cytotoxicity assays were performed along with the quantification of antioxidant enzymes, namely, catalase, superoxide dismutase (SOD) and reduced (GSH) and oxidized (GSSG) glutathione. We observed a decrease in viability and proliferation of MCF-7 cells, at higher concentrations of PPE, with no influence in epithelial cells. Interestingly, in a concentration-dependent manner, PPE triggered a significant decrease in migration on both cell lines, with a more pronounced effect in breast cancer cell line. Regarding antioxidant enzyme activity, on tumor cells higher concentrations of PPE decreased catalase activity and significantly increased SOD activity. Regarding GSH and GSSG, we observed different expression levels between MCF-7 and MCF-10A, with MCF-7 presenting lower levels compared to MCF-10A. GSH/GSSG ratio was notably higher in MCF-7 at 5 mM GAE. PPE exhibits anti-tumor effects without significantly affecting normal epithelial cells. Our work strengthens the potential antitumoral effect of PPE by reducing MCF-7 cell viability and proliferation through the imbalance of antioxidant enzymes.

Significance of Singlet Oxygen Molecule in Pathologies.

Reactive oxygen species, including singlet oxygen, play an important role in the onset and progression of disease, as well as in aging. Singlet oxygen can be formed non-enzymatically by chemical, photochemical, and electron transfer reactions, or as a byproduct of endogenous enzymatic reactions in phagocytosis during inflammation. The imbalance of antioxidant enzymes and antioxidant networks with the generation of singlet oxygen increases oxidative stress, resulting in the undesirable oxidation and modification of biomolecules, such as proteins, DNA, and lipids. This review describes the molecular mechanisms of singlet oxygen production in vivo and methods for the evaluation of damage induced by singlet oxygen. The involvement of singlet oxygen in the pathogenesis of skin and eye diseases is also discussed from the biomolecular perspective. We also present our findings on lipid oxidation products derived from singlet oxygen-mediated oxidation in glaucoma, early diabetes patients, and a mouse model of bronchial asthma. Even in these diseases, oxidation products due to singlet oxygen have not been measured clinically. This review discusses their potential as biomarkers for diagnosis. Recent developments in singlet oxygen scavengers such as carotenoids, which can be utilized to prevent the onset and progression of disease, are also described.

The combined effects of GSTM1/GSTT1 and MTHFR C677T polymorphisms on the systemic arterial hypertension susceptibility: A genetic association study in Brazilian diabetic patients

This genetic association study included 150 hypertensive diabetic patients and 150 normotensives non-diabetic subjects. Glutathione S-transferases M1 and T1 (GSTM1/GSTT1) deletion polymorphisms and methylenetetrahydrofolate reductase (MTHFR) C677T SNP (rs1801133) genotyping were performed by SYBR Green multiplex real-time and RFLP-PCR, respectively. Both GSTM1 and GSTT1 null (OR = 4.52, p = 0.04, and OR = 4.27, p = 0.01) and mutant (677TT) genotypes (OR = 2.95, p = 0.02) conferred risk to hypertension susceptibility. The combined genotypes (MTHFR:GSTT1:GSTM1) revealed a significant association: W/−/+, W/+/−, H/−/−, H/−/+, M/+/−, and M/+/+. These findings suggesting a probable oxidative hypothesis for hypertensive diabetic patients from the interaction of the detoxification mechanism and the homocysteine metabolism. The imbalance in antioxidant enzymes contributes to the establishment of oxidative stress in conjunction with hyperhomocysteinemia and reactive oxygen species production. We concluded that these findings suggest that both polymorphisms may contribute to hypertension susceptibility in diabetic patients.

The Genetic Diversity and Dysfunctionality of Catalase Associated with a Worse Outcome in Crohn's Disease.

Chronic gut inflammation in Crohn’s disease (CD) is associated with an increase in oxidative stress and an imbalance of antioxidant enzymes. We have previously shown that catalase (CAT) activity is permanently inhibited by CD. The purpose of the study was to determine whether there is any relationship between the single nucleotide polymorphisms (SNPs) in the CAT enzyme and the potential risk of CD associated with high levels of oxidative stress. Additionally, we used protein and regulation analyses to determine what causes long-term CAT inhibition in peripheral white mononuclear cells (PWMCs) in both active and inactive CD. We first used a retrospective cohort of 598 patients with CD and 625 age-matched healthy controls (ENEIDA registry) for the genotype analysis. A second human cohort was used to study the functional and regulatory mechanisms of CAT in CD. We isolated PWMCs from CD patients at the onset of the disease (naïve CD patients). In the genotype-association SNP analysis, the CAT SNPs rs1001179, rs475043, and rs525938 showed a significant association with CD (p < 0.001). Smoking CD patients with the CAT SNP rs475043 A/G genotype had significantly more often penetrating disease (p = 0.009). The gene expression and protein levels of CAT were permanently reduced in the active and inactive CD patients. The inhibition of CAT activity in the PWMCs of the CD patients was related to a low concentration of CAT protein caused by the downregulation of CAT-gene transcription. Our study suggests an association between CAT SNPs and the risk of CD that may explain permanent CAT inhibition in CD patients together with low CAT gene and protein expression.

Neuroprotective and anti-epileptic potentials of genus Artemisia L.

The Genus Artemisia L. is one of the largest genera in the Asteraceae family growing wild over in Europe, North America, and Central Asia and has been widely used in folk medicine for the treatment of various ailments. Phytochemical and psychopharmacological studies indicated that the genus Artemisia extracts contain various antioxidant and anti-inflammatory compounds and possess antioxidant, anti-inflammatory, antimicrobial, antimalarial, and antitumor activity. Recently, increasing experimental studies demonstrated that many Artemisia extracts offer a great antiepileptic potential, which was attributed to their bioactive components via various mechanisms of action. However, detailed literature on the antiepileptic properties of the genus Artemisia and its mechanism of action is segregated. In this review, we tried to gather the detailed neuroprotective and antiepileptic properties of the genus Artemisia and its possible underlying mechanisms. In this respect, 63 articles were identified in the PubMed and Google scholars databases, from which 18 studies were examined based on the pharmacological use of the genus Artemisia species in epilepsy. The genus Artemisia extracts have been reported to possess antioxidant, anti-inflammatory, neurotransmitter-modulating, anti-apoptotic, anticonvulsant, and pro-cognitive properties by modulating oxidative stress caused by mitochondrial ROS production and an imbalance of antioxidant enzymes, by protecting mitochondrial membrane potential required for ATP production, by upregulating GABA-A receptor and nACh receptor activities, and by interfering with various anti-inflammatory and anti-apoptotic signaling pathways, such as mitochondrial apoptosis pathway, ERK/CREB/Bcl-2 pathway and Nrf2 pathway. This review provides detailed information about some species of the genus Artemisia as potential antiepileptic agents. Hence, we recommend further investigations on the purification and identification of the most biological effective compounds of Artemisia and the mechanisms of their action to cure epilepsy and other neurological diseases.

Neuronal Metabolism and Neuroprotection: Neuroprotective Effect of Fingolimod on Menadione-Induced Mitochondrial Damage.

Imbalance in the oxidative status in neurons, along with mitochondrial damage, are common characteristics in some neurodegenerative diseases. The maintenance in energy production is crucial to face and recover from oxidative damage, and the preservation of different sources of energy production is essential to preserve neuronal function. Fingolimod phosphate is a drug with neuroprotective and antioxidant actions, used in the treatment of multiple sclerosis. This work was performed in a model of oxidative damage on neuronal cell cultures exposed to menadione in the presence or absence of fingolimod phosphate. We studied the mitochondrial function, antioxidant enzymes, protein nitrosylation, and several pathways related with glucose metabolism and glycolytic and pentose phosphate in neuronal cells cultures. Our results showed that menadione produces a decrease in mitochondrial function, an imbalance in antioxidant enzymes, and an increase in nitrosylated proteins with a decrease in glycolysis and glucose-6-phosphate dehydrogenase. All these effects were counteracted when fingolimod phosphate was present in the incubation media. These effects were mediated, at least in part, by the interaction of this drug with its specific S1P receptors. These actions would make this drug a potential tool in the treatment of neurodegenerative processes, either to slow progression or alleviate symptoms.

Sulphoraphane Supplementation Ameliorates Behavioural Impairments and Hippocampal Neurodegeneration Induced by Lead Exposure in Adult Wistar Rats

Lead (Pb) exposure induces oxidative stress causing imbalance in antioxidant enzymes, cognitive impairments and neurodegeneration. This study investigated the neuroprotective and antioxidant properties of sulphoraphane (SFN) on Pb-induced neurotoxicity of adult Wistar rats. Forty animals (150 ± 20 g) were divided into four groups (n=10): Group A received normal saline as placebo; Group B received 50 mg/kg body weight (bw) of Lead only; Group C received a combination of 50 mg/kg bw of Lead and 50 mg/kg bw of SFN; Group D received 50 mg/kg bw of SFN only. All administration was through oral gavages for 28 days; animals underwent behavioural tests (Morris water and Y- mazes); and thereafter sacrificed and brains extracted. Biochemical estimations of antioxidants (superoxide dismutase, reduced glutathione, and catalase), oxidative stress markers (malondialdehyde, nitric oxide, and hydrogen peroxide), neurotransmitters (dopamine, serotonin, and norepinephrine) and hippocampal histology were done. The results showed significant increase in escape latency, norepinephrine and oxidative stress markers with concomitant decrease percentage correct alternation, serotonin, dopamine and antioxidant enzymes in Pb exposed rats compared with the control. However, the co-administration of SFN and Pb significantly attenuated Pb neurotoxicity. Sulphoraphane is capable of ameliorating oxidative stress induced neurobehavioural deficits and hippocampal neurochemistry caused by Pb exposure in Alzheimer’s type animal model of neurodegenerative disorder.

Methanolic extract of Nepeta paulsenii as an ameliorative agent against CCl4 induced testicular damage in male albino rats

The issue of male sexual dysfunction arises due to numerous complications linked with sperm motility, imbalance of antioxidant enzymes and hormonal levels. Carbon tetrachloride (CCl4) is widely used as a standard toxin to induce chemical injury and toxicity. A lot of research has been performed on many species of the genus Nepeta in vitro and in vivo but the plant Nepeta paulsenii have been rarely used in this aspect. The current research was designed to explore the impacts of methanolic extract of the Nepeta paulsenii plant on CCl4 induced testicular impairment in male albino rats. Forty-eight rats were distributed equally into 8 groups; Control, Vehicle control, CCl4 treated (1 ml/kg), CCl4 + Silymarine treated, CCl4 + Nepeta paulsenii (200 mg/kg) treated, CCl4 + Nepeta paulsenii (400 mg/kg), Nepeta paulsenii (200 mg/kg) and Nepeta paulsenii (400 mg/kg) treated. Blood and testicles were obtained and analyzed. To check antioxidant enzymes, hormonal concentrations, daily sperm production (DSP), protein content and histopathology various analyses were performed. CCl4 exposure resulted in adverse morphological changes and significant (p < 0.05) reduction in testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH) concentrations, the activity of catalase (CAT), peroxidase (POD), superoxide dismutase (SOD), glutathione-disulfide reductase (GSR) and glutathione S-transferase (GST) enzymes, daily sperm production (DSP), protein content and high-density lipoproteins (HDL). CCl4 increased the TBARS and H2O2 production along with the cholesterol, triglyceride and low-density lipoproteins (LDL) levels, but Nepeta paulsenii restored these changes back to their normal state significantly (p < 0.05). Therefore, it was concluded that Nepeta paulsenii extract has potential to ameliorate the CCl4 induced testicular damage.

Catalase (antioxidant enzyme) activity in streptozotocin-induced diabetic rats

Background: High concentration and/or inadequate removal of reactive oxygen species may result in oxidative stress thatmay cause severe metabolic malfunction. An imbalance in antioxidant enzymes has been related to specific pathologies suchas diabetic complications. Catalase catalyzes the reduction of hydroperoxides, thereby protecting mammalian cells againstoxidative damage. In addition, catalase is active in neutralizing reactive oxygen species and so removes cellular superoxideand peroxides before they react with metal catalysts to form more reactive species. We investigated the status of catalaseactivity in erythrocytes of streptozotocin (STZ)-induced diabetic rats. Method: Catalase activity was measured by usingspectrophtometric techniques. Result: Catalase activity increased in diabetic rats compared to control group [25.7 ± 2.8 vs.16.3 ± 2.1 mmol H2O2 per min/ mg of protein, mean ± SD, p < 0.05]. Our results show that catalase activity increasedsignificantly in the erythrocytes of STZ-induced diabetic rats. (Int J Diabetes Metab 15: 22-24, 2007)

Pendimethalin induces oxidative stress, DNA damage, and mitochondrial dysfunction to trigger apoptosis in human lymphocytes and rat bone-marrow cells.

Pendimethalin (PM) is a dinitroaniline herbicide extensively applied against the annual grasses and broad-leaved weeds. There is no report available on PM-induced low-dose genotoxicity in human primary cells and in vivo test models. Such data gap has prompted us to evaluate the genotoxic potential of PM in human lymphocytes and rats. PM selectively binds in the minor groove of DNA by forming covalent bonds with G and C nitrogenous bases, as well as with the ribose sugar. PM induces micronucleus formation (MN) in human lymphocytes, indicating its clastogenic potential. Comet assay data showed 35.6-fold greater DNA damage in PM (200μM)-treated human lymphocytes. Rat bone-marrow cells, at the highest dose of 50mg/kg bw/day of PM also exhibited 10.5-fold greater DNA damage. PM at 200μM and 50mg/kg bw/day induces 193.4 and 229% higher reactive oxygen species generation in human lymphocytes and rat bone-marrow cells. PM-treated human lymphocytes and rat bone-marrow cells both showed dysfunction of mitochondrial membrane potential (ΔΨ m). PM exposure results in the appearance of 72.2 and 35.2% sub-G1 apoptotic peaks in human lymphocytes and rat bone-marrow cells when treated with 200μM and 50mg/kg bw/day of PM. Rats exposed to PM also showed imbalance in antioxidant enzymes and histological pathology. Overall, our data demonstrated the genotoxic and apoptotic potentials of PM in human and animal test models.

P53, MAPKAPK-2 and caspases regulate nickel oxide nanoparticles induce cell death and cytogenetic anomalies in rats

The unique properties of nickel oxide nanoparticles (NiO-NPs) distinguish it from traditional nickel containing materials, and enable its industrial application as an advanced nanomaterial. Despite the benefits, the in vivo toxicological studies on NiO-NPs have been mainly focused on its pulmonary pathology. However, NiO-NPs exposure via oral route and its subsequent toxic effects in exposed animals are still lacking. Hence, we evaluated the NiO-NPs oral toxicity in male Wistar rats. NiO-NPs induced significant increase in chromosomal aberrations (CAs), micronuclei (MN) formation and, DNA damage in rats. Flow cytometric analysis showed apoptosis, ROS generation and dysfunction of mitochondrial membrane potential (ΔΨm). Imbalance of antioxidant enzymes, along with histological alterations was found in liver. Taking together, these results unequivocally suggested that NiO-NPs induced toxicity was through cyto-genetic alterations, oxidative stress, apoptosis and liver toxicity. The western blotting data validated the interplay of p53 and MAPKAPK-2 signalling via activation of caspases 8, 3, cyto c, pro-apoptotic bax and anti-apoptotic bcl-2 proteins.

1,25-Dihydroxyvitamin D3 prevents deleterious effects of homocysteine on mitochondrial function and redox status in heart slices

Because homocysteine (Hcy) is a risk factor for cardiovascular disease, and vitamin D deficiency can contribute to cardiovascular pathologies. In the present study, we tested the hypothesis that Hcy could impair energy metabolism, mitochondrial function, and redox status in heart slices of Wistar rats and that 1,25-dihydroxivitamin D3 (calcitriol) treatment could prevent such effects. Heart slices were first pretreated with 3 different concentrations of calcitriol (50, 100, and 250nmol/L) for 30minutes at 37°C, after which Hcy was added to promote deleterious effects on metabolism. After 1 hour of incubation, the samples were washed, homogenized, and stored at −80°C before analysis. The results showed that Hcy caused changes in energy metabolism (respiratory chain enzymes), mitochondrial function, and cell viability. Homocysteine also induced oxidative stress, increasing lipid peroxidation, reactive oxygen species generation, and protein damage. An imbalance in antioxidant enzymes was also observed. Calcitriol (50nmol/L) reverted the effect of Hcy on the parameters tested, except for the immunocontent of catalase. Both treatments (calcitriol and Hcy) did not alter the vitamin D receptor immunocontent, which combined with the fact that our ex vivo model is acute, suggesting that the beneficial effect of calcitriol occurs directly through antioxidative mechanisms and not via gene expression. In this study, we show that Hcy impairs mitochondrial function and induces changes in the redox status in heart slices, which were reverted by calcitriol. These findings suggest that calcitriol may be a preventive/therapeutic strategy for complications caused by Hcy.

Перекисне окислення білків та ліпідів при недиференційованій дисплазії сполучної тканини у дітей

Aim: The study of lipid and protein peroxidation in children with undifferentiated connective tissue dysplasia. Materials and Methods: There were studied the state of lipid and protein peroxidation on 63 children (33 children with undifferentiated connective tissue dysplasia (UDCTD) and 30 children without (UDCTD)) by spectrofotometrie (the change of index and the end product of lipid peroxide modification — malondialdehyde (MDA) in blood plasma and erythrocyte membranes, the process of peroxidation of proteins (PSP) — the content of the final products of oxidative modification — 2,4 dinitrophenylhydrazine blood plasma, the activity of the antioxidant defense enzymes — catalase (CT) and superoxide dismutase (SOD) activity in membrane structures and plasma) and biochemical methods (level of free cholesterol). Results: we established a significant increase in venous blood plasma products of lipid peroxidation, an increase of lipid peroxidation products in erythrocytes and an imbalance in the antioxidant defense system in children with UDCTD compared with a group of children without UDCTD. Conclusion: there were observed changes in the peroxidation of plasma proteins in venous blood (2,4 dinitrophenylhydrazine in apoproteids of lipoproteins low and very low density), the index of peroxide modification of lipoproteins and lipid membranes of red blood cells, an imbalance of antioxidant enzymes (SOD and CT), which the extent is correlated with the degree of phenotypic disorders in UDCTD in adolescents with UDCTD. Key words: children, undifferentiated connective tissue dysplasia, lipid peroxidation, protein peroxidation, antioxidant enzymes.

Neuroprotective effect of Spirulina fusiform and amantadine in the 6-OHDA induced Parkinsonism in rats.

BackgroundMulti-factorial etiology exists in pathophysiology of neurodegenerative diseases. The imbalance of anti-oxidant enzymes and dopamine level leads to Parkinsonism. The objective of this study was to assess the protective effect of Spirulina fusiform alone and in combination with amantadine against Parkinsonism effect in 6-hydroxydopamine (6-OHDA) induced rat model.MethodsS. fusiform was administered in different groups (500 mg/kg, once daily and twice daily) and a combination of spirulina (500 mg/kg, once daily) with amantadine (20 mg/kg once daily) for 30 days before and 14 days after a single injection of 6-OHDA into the dorsal striatum. Post lesion produced rotational behavior which was measured at two week intervals (37th and 44th day). Locomotors activity was also done at 44th and muscle coordination at 48th day. Dorsal striatum was isolated from rat brain for evaluating the antioxidant assays and dopamine content at 49th day.ResultsBoth the body rotations (ipsilateral and contralateral) were found to have a statistically significant (p < 0.001) decrease by 34.26 and 52 % after treatment with spirulina (Twice a day) in spirulina treated lesioned group. A higher percentage of improvement was shown in the reduction of ipsilateral (57.34 %) and contralateral (78.3 %) rotations in combination of spirulina with amantadine treated lesioned group rather than spirulina alone treated lesioned groups when compared with positive control lesioned group. Body movements and locomotor activity were improved statistically (p < 0.0001) significant in both treated lesioned groups (Combination of spirulina with amantadine and spirulina twice daily). Similar results were also seen in anti-oxidant levels which later on reached to the normal value. The levels of dopamine content had a statistically significant (p < 0.0001) increase by 78.3 % only in case of spirulina with amantadine treated lesioned group.ConclusionSpirulina is a potent nutraceutical supplement all over the world, so my preclinical study may contribute to give an additional adjuvant drug therapy in aging related disorders (Neurodegenerative as well as diabetes associated neurodegenerative disorders).Electronic supplementary materialThe online version of this article (doi:10.1186/s12906-015-0815-0) contains supplementary material, which is available to authorized users.

Morin hydrate attenuates the acrylamide-induced imbalance in antioxidant enzymes in a murine model.

Liver diseases are among the most serious health issues nowadays. Hepatocellular carcinoma, one of the most lethal types of cancer worldwide, can be caused by chemically-induced oxidative stress. In the present study, we aimed to evaluate the protective effects of morin hydrate (MH) against acrylamide (AA)-induced hepatotoxicity in male ICR mice. The mice were randomly allocated into 4 groups [the control, the group subcutaneously injected with AA alone (50 mg/kg body weight), the group subcutaneously injected with AA (50 mg/kg body weight) and MH (5 mg/kg body weight) and the group subcutaneously injected with AA (50 mg/kg body weight) and MH (15 mg/kg body weight) for 5 consecutive days]. Histopathological evaluations were performed and the levels of serum hepatic enzymes were analyzed to determine initial liver injury, and the mice in the AA-treated groups were compared with the mice receiving no treatment and with the mice administered MH in combination with AA. Furthermore, oxidative stress, hepatic inflammation and the levels of DNA damage-related markers were evaluated to determine the extent of liver damage induced by AA within a short-term period. The subcutaneous administration of AA induced severe hepatic injury, and combined treatment with AA and MH resulted in a significant improvement in all evaluated parameters. This recovery was most obvious in the group receiving AA and 15 mg/kg body weight dose of MH. The findings of our study demonstrated that MH protected mice from severe hepatic injury induced by AA. Moreover, MH is a natural polyphenolic compound, and thus it has potential for use in the treatment of severe liver diseases, in place of many synthetic drugs.

Antitumor activity of C-phycocyanin from Arthronema africanum (Cyanophyceae)

ABSTRACT Pure C-phycocyanin (C-PC) was isolated from Arthronema africanum to evaluate its potential antitumor effects in vivo and in vitro. Experimental myeloid Graffi tumor in hamsters was used as a model. The cell proliferation assay showed that C-PC treatment, at concentration of 100 µg mL -1 for 24 h, significantly inhibited the growth of Graffi tumor cells (51.4% viability). Agarose gel electrophoresis of the genomic DNA of treated cells displayed time- and concentration-dependent fragmentation pattern, typical for apoptosis. Apoptotic process was related to the increase in cellular manganese and copper/zinc superoxide dismutases and glutathione reductase activities, coupled with a low catalase activity. In vivo C-PC administration (5.0 mg kg -1 body weight) suppressed the tumor transplantability and growth, while the mean survival time of the tumor-bearing hamsters was increased. The results revealed promising antitumor activities of A. africanum C-PC and suggested the potential of this natural biliprotein pigment for future pharmacological and medical applications. The study provided new data on the mechanism of the C-PC-induced apoptosis in which the imbalance of antioxidant enzymes that favoured hydrogen peroxide accumulation might play a leading role. Key words: Antitumor activity, Arthronema africanum , In vivo , In vitro , C-pycocyanin, Myeloid Graffi tumor

Oxidative stress in early stage Bipolar Disorder and the association with response to lithium

BackgroundSeveral studies have described increased oxidative stress (OxS) parameters and imbalance of antioxidant enzymes in Bipolar Disorder (BD) but few is know about the impact of treatment at these targets. However, no study has evaluated OxS parameters in unmedicated early stage BD and their association with lithium treatment in bipolar depression. MethodsPatients with BD I or II (n = 29) in a depressive episode were treated for 6 weeks with lithium. Plasma samples were collected at baseline and endpoint, and were also compared to age-matched controls (n = 28). The thiobarbituric acid reactive substances (TBARS), and the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities were measured. ResultsSubjects with BD depression at baseline presented a significant increase in CAT (p = 0.005) and GPx (p < 0.001) levels, with lower SOD/CAT ratio (p = 0.001) and no changes on SOD or TBARS compared to healthy controls. Regarding therapeutics, lithium only induced a decrease in TBARS (p = 0.023) and SOD (p = 0.029) levels, especially in BDII. Finally, TBARS levels were significantly lower at endpoint in lithium responders compared to non-responders (p = 0.018) with no difference in any biomarker regarding remission. ConclusionThe present findings suggest a reactive increase in antioxidant enzymes levels during depressive episodes in early stage BD with minimal prior treatment. Also, decreased lipid peroxidation (TBARS) levels were observed, associated with lithium's clinical efficacy. Overall, these results reinforce the role for altered oxidative stress in the pathophysiology of BD and the presence of antioxidant effects of lithium in the prevention of illness progression and clinical efficacy.

Increased Oxidative Stress and Imbalance in Antioxidant Enzymes in the Brains of Alloxan-Induced Diabetic Rats

Diabetes Mellitus (DM) is associated with pathological changes in the central nervous system (SNC) as well as alterations in oxidative stress. Thus, the main objective of this study was to evaluate the effects of the animal model of diabetes induced by alloxan on memory and oxidative stress. Diabetes was induced in Wistar rats by using a single injection of alloxan (150 mg/kg), and fifteen days after induction, the rats memory was evaluated through the use of the object recognition task. The oxidative stress parameters and the activity of antioxidant enzymes, superoxide dismutase (SOD), and catalase (CAT) were measured in the rat brain. The results showed that diabetic rats did not have alterations in their recognition memory. However, the results did show that diabetic rats had increases in the levels of superoxide in the prefrontal cortex, and in thiobarbituric acid reactive species (TBARS) production in the prefrontal cortex and in the amygdala in submitochondrial particles. Also, there was an increase in protein oxidation in the hippocampus and striatum, and in TBARS oxidation in the striatum and amygdala. The SOD activity was decreased in diabetic rats in the striatum and amygdala. However, the CAT activity was increased in the hippocampus taken from diabetic rats. In conclusion, our findings illustrate that the animal model of diabetes induced by alloxan did not cause alterations in the animals' recognition memory, but it produced oxidants and an imbalance between SOD and CAT activities, which could contribute to the pathophysiology of diabetes.

An imbalance in antioxidant enzymes and stress proteins in childhood asthma

Objectives: The study was undertaken to examine antioxidant status and level of the major intracellular heat shock proteins (Hsps) in healthy children and children with mild and moderate asthma. Design and methods: Native gel assays were performed to estimate activities of copper/zinc (CuZn) and manganese (Mn) superoxide dismutase (SOD), and catalase (CAT) in peripheral blood mononuclear cells (PBMC) of healthy and asthmatic children. Hsp70 and Hsp90 protein levels in PBMCs were assessed by Western blot analysis. Results: Moderate asthmatics displayed higher CuZnSOD/CAT activity ratio compared to healthy children, and increased Hsp90 level compared to mild asthmatics and healthy children. Conclusions: With regard to the imbalance in the antioxidant enzyme activities children with moderate asthma differ from healthy children, while an increased Hsp90 expression could be associated with the disease severity, as well.

Molecular Mechanisms Mediating Inhibition of Human Large Conductance Ca 2+ -Activated K + Channels by High Glucose

Diabetic vascular dysfunction is associated with an increase in reactive oxygen species (ROS). In this study, we hypothesized that hyperglycemia-induced ROS generation would impair the function of large conductance Ca(2+)-activated K(+) (BK) channels, which are major determinants in vasorelaxation. We found that when cultured in high glucose (HG) (22 mmol/L), HEK293 cells showed a reduction in expressed hSlo current densities, as well as slowed activation and deactivation kinetics. When human coronary smooth muscle cells were cultured in HG, similar findings were observed for the BK currents. HG enhanced superoxide dismutase and suppressed catalase (CAT) expression in HEK293 cells, leading to a significant increase in intracellular ROS. The effects of HG were mimicked by hydrogen peroxide (H(2)O(2)), and hSlo functions were restored by CAT gene transfer. Peroxynitrite inhibited hSlo current density but did not change channel kinetics. The hSloC911A mutant was insensitive to the effects of HG and H(2)O(2). Hence, imbalance of antioxidant enzymes plays a critical role in ROS generation in HG, impairing hSlo functions through H(2)O(2)-dependent oxidation at cysteine 911. This may represent an important fundamental mechanism that contributes to the impairment of vasodilation in diabetes.