Decreased Glutathione Reductase Activity Research Articles

Исследование активности глутатионредуктазы в коре головного мозга, стволе мозга и мозжечке облучённых крыс

The paper presents results of the study of pressing problems related to molecular mechanisms of radiation effects on a human body, as well as radiation protection and safety control to human beings in healthcare settings. Results of research on activity of glutathione reductase, the enzyme of the antioxidant system, in various structural-functional brain areas in the white outbred rats exposed to whole-body gamma radiation at a dose of 6 Gy are considered. Glutathione reductase activity was found in the cerebral cortex, brain stem and cerebellum of irradiated animals. The activity of glutathione reductase in the cytoplasm was higher than in mitochondria derived from cortex, cerebellum and brain stem cells in the intact animals. The sharp decrease in glutathione reductase activity was observed on the 7th day after the exposure of rats to gamma radiation. The activity of glutathione reductase in the studied brain areas of irradiated rats changes with the time of radiation lesion development. The role of the enzyme in the metabolism of glutathione, a substrate of glutathione reductase, in rats brain undergone acute whole-body radiation injury, is discussed.

New approaches to the typology and prediction of the effectiveness of therapy for late-life depression

To analyze clinical parameters and effectiveness of therapy in depressed patients of late age with different activity of enzymes of energy, glutamate metabolism and antioxidant glutathione system in platelets and red blood cells. The study included 53 hospitalized patients (41 women and 12 men), aged 60 to 86 years (median - 66 years), with a depressive episode of mild to marked severity within the framework of recurrent depressive disorder, bipolar affective disorder or a single depressive episode according to ICD-10. The patients were examined using clinical, psychometric, biochemical and statistical methods. Psychometric assessment of patients' condition was performed before the start of therapy and on the 28th day of treatment using HAMD-17 and HARS. Blood sampling was carried out to determine the activity of cytochrome c-oxidase (COX), glutathione reductase (GR), glutathione S-transferase (GST) and glutamate dehydrogenase (GDH). Cluster analysis revealed 3 clusters (Cl.1, Cl.2, Cl.3), which differed in biochemical indicators. In Cl.1 (n=24, 45.2%), there was a decrease in the activity of COX (p<0.05) and a decrease of GR activity in red blood cells and GST activity in platelets (p<0.001). Patients of Cl.2 (n=11, 20.8%) had increased COX activity (p<0.001) and decreased GDH activity (p<0.001). In patients of Cl.3 (n=18, 34%) the enzyme activity was similar to that in the controls. Later age at disease onset was observed in Cl.1 compared to Cl.2 (51 years [40; 60.5] and 32 years [19; 59], p=0.052). Compared with Cl.2 and Cl.3, patients of Cl.1 significantly more often (p<0.05) had apathetic depressions (41.7%), while complex depressions were observed almost 2 times less often than in Cl.2 (50% and 91.9%, p<0.05). The effectiveness and tolerability of psychopharmacotherapy was higher in Cl.3. There is a relationship between the nature of changes in metabolic parameters and differences in the phenomenology and course of late-age depression. The results of the study open up new directions in the field of predicting the effectiveness of therapy and the development of personalized therapeutic approaches to improve the effectiveness and safety of treatment of depressed elderly patients.

Association of genetic variants in the GPX1 and GPX4 genes with the activities of glutathione-dependent enzymes, their interaction with smoking and the risk of acute pancreatitis

Genetic factors and tobacco smoke exposure can be associated with an increased risk of acute pancreatitis (AP). The pathogenesis of AP is associated with intensive oxidative stress. Glutathione peroxidase (GPx) is one of many enzymes involved in the neutralization of free radicals. This study aimed to investigate the impact of SNP rs1050450 in the GPX1 gene and rs713041 in the GPX4 gene on the activity of total GPx in a group of AP patients and healthy subjects. It was found that AP can contribute to decreased GPx activity (in plasma and erythrocyte lysate) accompanied by an increased glutathione reductase (GR) activity and decreased glutathione (GSH) concentration in two groups, non-smokers and smokers. A decreased GPx activity in erythrocyte lysate of AP patients compared to healthy subjects was associated with the occurrence of the CC genotype for SNP rs1050450. It was noted an increased GPx activity and decreased GR activity in erythrocytes of non-smoking AP patients with the TT genotype compared to subjects with the CC and TC genotype for SNP rs713041. However, in the group of smoking AP patients with this genotype, GR activity was elevated compared to non-smokers, which was accompanied by increased GSH concentration. These results can indicate that smoking in the course of AP can change the involvement of antioxidants in dependence on the genotype for the examined SNPs. The CC genotype for SNP rs1050450 and the TT genotype for rs713041 increases the risk of AP recurrence, which may be associated with increased MDA concentration.

Herb Sanqi-Derived Compound K Alleviates Oxidative Stress in Cultured Human Melanocytes and Improves Oxidative-Stress-Related Leukoderma in Guinea Pigs.

Sanqi, a traditional Chinese herb, is widely used for cardiovascular diseases, and its neuroprotective effects against oxidative stress were recently discovered. The purpose of this study was to investigate whether Sanqi-derived compound K (Sanqi-CK), an active metabolite of Sanqi, could protect melanocytes from oxidative stress. Cultured human primary skin epidermal melanocytes (HEMn-MPs) were treated with hydrogen peroxide (H2O2) in the presence or absence of Sanqi-CK. Sanqi-CK exhibited protective effects against H2O2-induced cell death by reducing oxidative stress. In addition, treatment with Sanqi-CK reversed the decreased glutathione reductase activity and decreased ratio of reduced glutathione (GSH)/oxidized glutathione (GSSG) seen in H2O2-treated melanocytes. Furthermore, topical application of Sanqi-CK alleviated leukoderma in guinea pigs, a disorder characterized by melanocyte cell death resulting from rhododendrol-induced oxidative stress. Taken together, these data suggest that Sanqi-CK protects melanocytes against oxidative stress, and its protective effects are associated with modulating the redox balance between GSH and GSSG and activating glutathione reductase. Thus, Sanqi-CK may be a good candidate for preventing melanocyte loss in oxidative-stress-associated pigmentary disorders.

Evaluation of glutathione reductase activity in colon tissue of patients with irritable bowel syndrome.

Irritable bowel syndrome (IBS) is known as one of the most common irritating gastrointestinal disorders. The mechanism behind IBS is still under investigation and it is thought that it may arose from multi factors among which free radicals have been previously mentioned. Studies have found an association between oxidative stress and IBS; however, little is known about the mechanisms and oxidative stress components status during IBS. One of the key factors playing a central role in oxidative stress network is glutathione reductase (GR). Here we report the GR activity in colon tissue samples during IBS to explore a part of contributing components in IBS pathogenesis. The GR enzyme activity was measured in 15active IBS colon biopsy samples and was compared to our best available age and sex matched colorectal tissue samples from normal marginal tissue of resected colon cancers (n=15). The enzyme activity in the two groups was determined and compared using a commercial GR Assay Kit (Cayman chemical). A significant decrease in GR activity among IBS tissue samples was observed compared to anatomically normal marginal colon tissue samples (p=0.007). Lower GR activity may increase oxidized glutathione there by in turn could contribute as a main component in oxidative stress network. The lower GR activity results in hampered defense mechanism against produced free radical species. This finding may clarify a part of IBS pathogenesis.

The relationship of folate deficiency, hyperhomocysteinemia and glutathione metabolism in hypertensive patients

Hypertension (HTN) is often accompanied by folic acid (FA) deficiency and hyperhomocysteinemia (HHcy). Reduced glutathione (GSH) and dependent enzymes determine the state of cellular antioxidant and redox systems in cardiovascular pathology. The aim of our work is to assess the relationship between the status of FA and the presence of HHcy with enzymes of glutathione metabolism and the redox state of erythrocyte glutathione in HTN. Design and methods. In blood plasma samples from 43 HTN patients admitted to the clinic of Pavlov University, the concentration of FA and total homocysteine (oHcy) was determined. We also evaluated the level of GSH, the activity of glutathione peroxidase and glutathione reductase (GR) in erythrocytes. Results. In the whole group, GR activity positively correlated with the concentration of FA (R = 0,415; p = 0,001). A significant decrease in GR activity (U/g Hb) was found in the subgroup with the low level of FA [0,8 (0,5–1,1)] compared with the subgroup without a FA deficiency [1,2 (0,9–2,0)]. The GSH level (μM/g Hb) was also lower (p &lt; 0,018) in the subgroup with FA deficiency [1,3 (0,9–2,1)] compared with the subgroup with normal FA levels [1,8 (1,5–4,6)]. A significant decrease in the level of GSH and GR activity in the subgroup with HHcy was found compared with the corresponding parameters in the subgroup without HHcy. However, even in the absence of HHcy patients with FA deficiency demonstrated a significant decrease in GR activity compared to patients without FA deficiency. In this case, GR positively correlated with FA (R = 0,564; p = 0,03). Conclusions. The deficiency of FA can increase the deficiency of GR activity, regardless of the level of oHcy. The indicator of GR activity in erythrocytes can be considered as a possible marker of functional deficiency of FA in the absence of HHcy.

Prior exercise protects against oxidative stress and motor deficit in a rat model of Parkinson's disease.

This study investigated if a prior long-term physical exercise protocol protects the substantia nigra and the striatum against oxidative stress and motor deficits in a Parkinson Disease model induced by 6-hydroxydopamine. Three animal treatment groups were included in the study: sham; 6-hydroxydopamine and 6-hydroxydopamine/exercise. Previously to the intrastriatal lesion by 6-hydroxydopamine, rats in the exercise groups performed a swimming program for 18weeks. The rats were submitted to behavioral tests before and after intrastriatal 6-hydroxydopamine injection. The oxidative stress was analyzed by Thiobarbituric Acid Reactive Substances and Glutathione reductase activity methods. The exercise decreased lipid peroxidation and increased glutathione reductase activity in the substantia nigra. In contrast, in the striatum, exercise increased lipid peroxidation and decreased glutathione reductase activity. Exercise increased contralateral rotations and reduces immobility levels at 14days post lesion. The exercise prior to 6-OHDA lesion had protective action only in substantia nigra against oxidative stress.

Effects of Acute Ethanol Administration on Brain Oxidative Status: The Role of Acetaldehyde.

Ethanol (EtOH), one of the most widely consumed substances of abuse, can induce brain damage and neurodegeneration. EtOH is centrally metabolized into acetaldehyde, which has been shown to be responsible for some of the neurophysiological and cellular effects of EtOH. Although some of the consequences of chronic EtOH administration on cell oxidative status have been described, the mechanisms by which acute EtOH administration affects the brain's cellular oxidative status and the role of acetaldehyde remain to be elucidated in detail. Swiss CD-I mice were pretreated with the acetaldehyde-sequestering agent d-penicillamine (DP; 75mg/kg, i.p.) or the antioxidant lipoic acid (LA; 50mg/kg, i.p.) 30minutes before EtOH (2.5g/kg, i.p.) administration. Animals were sacrificed 30minutes after EtOH injection. Glutathione peroxidase (GPx) mRNA levels; GPx and glutathione reductase (GR) enzymatic activities; reduced glutathione (GSH), glutathione disulfide (GSSG), glutamate, g-L-glutamyl-L-cysteine (Glut-Cys), and malondialdehyde (MDA) concentrations; and protein carbonyl group (CG) content were determined in whole-brain samples. Acute EtOH administration enhanced GPx activity and the GSH/GSSG ratio, while it decreased GR activity and GSSG concentration. Pretreatment with DP or LA only prevented GPx activity changes induced by EtOH. Altogether, these results show the capacity of a single dose of EtOH to unbalance cellular oxidative homeostasis.

Effects of ibogaine per os treatment on redox homeostasis in rat kidney

Our previous results showed that a single oral dose (1 or 20 mg/kg body weight) of the anti-addiction agent ibogaine induced in rats 6 and 24 h after administration glycogenolytic activity in hepatocytes, followed by a mild oxidative stress. In this work, we examined the in vivo effect of the same doses of ibogaine on rat kidney morphology, antioxidant enzyme (superoxide dismutases (SOD1 and 2), catalase, glutathione peroxidase, glutathione reductase (GR) and glutathione- S-transferase) activities, and oxidative stress (TBARS) and redox (-SH groups) parameters. The dose of 1 mg/kg ibogaine induced an elevation in SOD1 activity and decreased GR activity after 6 and 24 h. GR activity was decreased at 6 and 24 h after 20 mg/kg ibogaine administration, suggesting changed redox homeostasis. After 24 h, we observed an increase in moderate morphological changes, without changes in urinalyses, indicating that kidney function was not measurably affected. Nevertheless, kidney-function monitoring during and following ibogaine use in human subjects is advisable.

Effects of Humic Acids in Chronic Lead Poisoning.

Chronic exposure to lead causes disruption to energy production mechanisms and tissue damage, in particular through its binding to thiol groups and competition for zinc binding sites. We investigated the possibility of preventing the consequences of chronic lead poisoning by administration of three different doses of humic acids (HAs) into feed with the aim of establishing an effective HA dose. During the 10-week experiment, a sub-lethal dose of lead acetate was given to rats during the first 5weeks, with continuous administration of HA over 10weeks. Measurements were taken to determine the content of the metals Pb, Mn, Cu, Fe and Zn; the metalloid Se; and selected antioxidant markers in the heart, liver, kidney and plasma after the first, fifth and tenth weeks of experiment. The administration of lead and HAs clearly affects the redistribution of the elements and the activity of the antioxidant enzymes. This fact was particularly highlighted in the lead-only group as, within the experiment, significantly higher Pb concentrations were found only in the plasma of this group. However, in the group with 1% HA administered with lead, we observed a rise in Zn concentrations in the organs and the deposition of Fe into the liver. Decreased glutathione reductase activity in the plasma and balanced reduced glutathione concentrations indicated sufficient efficiency of redox reactions. SOD activities were among those affected most strongly, with only the 1% HA group showing no effect on heavy metal redistribution as a result of HA administration.

Paljung-San, a traditional herbal medicine, attenuates benign prostatic hyperplasia in vitro and in vivo

Ethnopharmacological relevancePaljung-san is a traditional herbal medicine used widely for the treatment of urogenital diseases in East Asia. However, scientific evidence of the efficacy of Paljung-san and its mechanisms of action against benign prostatic hyperplasia (BPH) is not clearly established. Aim of the studyWe investigated the inhibitory effect of Paljung-san water extract (PSWE) and its mechanisms against BPH in vitro and in vivo. Materials and methodsActive compounds of PSWE were analyzed quantitatively by High-performance liquid chromatography (HPLC). For in vitro study, PSWE treated BPH-1 cells were used to perform western blot analysis, cell cycle analysis and enzyme-linked immunosorbent assay. For in vivo BPH model, male rats were subcutaneously injected with 10 mg/kg of testosterone propionate (TP) every day for four weeks. 200 and 500 mg/kg of PSWE was administrated daily by oral gavage with s.c. injection of TP, respectively. ResultsHPLC revealed that PSWE contains 1.21, 1.18, 2.27, 3.56, 4.23, 3.00, 6.78, and 0.004 mg/g of gallic acid, 5-caffeoylquinic acid, chlorogenic acid, geniposide, liquiritin apioside, liquiritin, glycyrrhizin, and chrysophanol components, respectively. In human BPH-1 cells, PSWE treatment reduced cell proliferation through arresting the cell cycle in the DNA synthesis phase. Moreover, PSWE suppressed prostaglandin E2 production with reduced cyclooxygenase-2 expression. In TP -induced BPH rat model, PSWE administration showed reduced prostate weights and dihydrotestosterone levels and led to a restoration of normal prostate morphology. PSWE also decreased TP-induced Ki-67 and cyclin D1 protein levels in the prostatic tissues. Decreased glutathione reductase activity and increased malondialdehyde levels in the BPH groups were reversed by PSWE administration. ConclusionPSWE attenuates the progression of BPH through anti-proliferative, anti-inflammatory and anti-oxidant activities in vitro and in vivo. Therefore, these data provide the scientific evidence of pharmacological efficacy of PSWE against BPH.

Glucose-6-phosphate dehydrogenase inhibition attenuates acute lung injury through reduction in NADPH oxidase-derived reactive oxygen species.

Acute lung injury (ALI) is a heterogeneous disease with the hallmarks of alveolar capillary membrane injury, increased pulmonary oedema and pulmonary inflammation. The most common direct aetiological factor for ALI is usually parenchymal lung infection or haemorrhage. Reactive oxygen species (ROS) generated by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX2) are thought to play an important role in the pathophysiology of ALI. Glucose-6-phosphate dehydrogenase (G6PD) plays an important role both in production of ROS as well as their removal through the supply of NADPH. However, how G6PD modulation affects NOX2-mediated ROS in the airway epithelial cells (AECs) during acute lung injury has not been explored previously. Therefore, we investigated the effect of G6PD inhibitor, 6-aminonicotinamide on G6PD activity, NOX2 expression, ROS production and enzymatic anti-oxidants in AECs in a mouse model of ALI induced by lipopolysaccharide (LPS). ALI led to increased G6PD activity in the AECs with concomitant elevation of NOX2, ROS, SOD1 and nitrotyrosine. G6PD inhibitor led to reduction of LPS-induced airway inflammation, bronchoalveolar lavage fluid protein concentration as well as NOX2-derived ROS and subsequent oxidative stress. Conversely, ALI led to decreased glutathione reductase activity in AECs, which was normalized by G6PD inhibitor. These data show that activation of G6PD is associated with enhancement of oxidative inflammation in during ALI. Therefore, inhibition of G6PD might be a beneficial strategy during ALI to limit oxidative damage and ameliorate airway inflammation.

Response of Triticum aestivum to boron stress

Despite the demonstration that proline accumulation and gene expression of Δ1-pyrroline-5-carboxylate synthase (p5cS) increased under osmotic stress, the impact of excess boron on proline metabolism is not well known. Therefore, we investigated the effect of different boron concentrations (10, 50, 70, 140 and 200 ppm) on seedlings root growth, lipid peroxidation rate, antioxidant enzyme activity (glutathione reductase (GR), ascorbate peroxidase (APX), catalase (CAT)), proline accumulation and transcription level of p5cS gene in Triticum aestivum L. AK-702. It was observed that seed germination and root growth in T. aestivum decreased depending on the concentration of boron. Our results indicated that boron toxicity induced lipid peroxidation and decreased GR activity under a high concentration of boron. However, the APX activity did not significantly change under high concentrations of boron (70, 140 and 200 ppm), while it increased under the lower levels of boron (10 and 50 ppm). In addition, excess boron enhanced CAT activity in the 200 ppm boron treated groups. Proline accumulation increased 2.25 and 1.45 fold in the 140 and 200 ppm boron applications. In addition, analyses of the mRNA transcription level using the semi-quantitative RTPCR results showed that excess boron increased the p5cS mRNA transcript levels and showed a positive correlation of these levels with proline accumulation in T. aestivum roots.

Subacute Toxicity Effects of Deltamethrin on Oxidative Stress Markers in Rainbow Trout.

Deltamethrin is a pyrethroid insecticide that is considered extremely toxic to aquatic organisms. We evaluated the effect of subacute doses (0.033, 0.1, or 0.3 mg/kg) of deltamethrin on micronucleus frequency and oxidative stress markers in Rainbow Trout Oncorhynchus mykiss at 1, 2, 3, 4, and 8 d after intracoelomic injection. No genotoxic damage was recorded, as no specimen showed a micronucleus number above the physiological range. Deltamethrin exposure elicited a transient reduction in the levels of superoxide dismutase, catalase, glutathione peroxidase, and glutathione S-transferase and a persistent decrease in glutathione reductase activity. Overall, the lower antioxidant enzyme activity in the deltamethrin-treated fish was mainly dose-dependent. Received May 27, 2016 accepted June 18, 2017.

Cylindrospermopsin effects on cell viability and redox milieu of Neotropical fish Hoplias malabaricus hepatocytes.

Cylindrospermopsin (CYN) is a cyanotoxin that is cytotoxic to a wide variety of cells, particularly to the hepatocytes. In this study, the toxic effects of purified CYN were investigated in primary cultured hepatocytes of Neotropical fish Hoplias malabaricus. After isolation, attachment, and recovery for 72h, the cells were exposed for 72h to 0, 0.1, 1.0, 10, and 100μgl-1 of CYN. Then, cell viability and a set of oxidative stress biomarker responses were determined. Catalase, superoxide dismutase, glucose-6-phosphate dehydrogenase, and glutathione S-transferase activities were not affected by exposure to CYN. Concentration-dependent decrease of glutathione reductase activity occurred for most CYN-exposed groups, whereas non-protein thiol content increased only for the highest CYN concentration. Lipid peroxidation, protein carbonylation, and DNA damage levels were not altered, but reactive oxygen species levels increased in the cells exposed to the highest concentration of CYN. Cell viability decreased in all the groups exposed to CYN. Thus, CYN may cause a slight change in redox balance, but it is not the main cause of cell death in H. malabaricus hepatocytes.

The effects of ciprofloxacin on early life stages of common carp (Cyprinus carpio).

The authors performed a toxicity test with ciprofloxacin in fertilized eggs of common carp according to guideline 210 of the Organisation for Economic Co-operation and Development. The tested concentrations were 1 μg L(-1) , 100 μg L(-1) , 500 μg L(-1) , 1000 μg L(-1) , and 3000 μg L(-1) . Accelerated hatching was found in all groups exposed to ciprofloxacin, but significant growth reduction was found only in the group exposed to the highest concentration (3000 μg L(-1) ). Increased numbers of macroscopic morphological anomalies were observed on day 6 of the test (after hatching). The highest numbers of macroscopic morphological anomalies were observed in the groups of free embryos and larvae exposed to ciprofloxacin concentrations of 100 μg L(-1) , 500 μg L(-1) , 1000 μg L(-1) , and 3000 μg L(-1) (20-23% of tested samples). A gradual decrease in glutathione S-transferase activity was detected in all experimental groups exposed to ciprofloxacin, but significant differences (p < 0.01) were found only in groups treated with 500 μg L(-1) and 3000 μg L(-1) . Glutathione peroxidase and catalase exhibited increased activity in most of the tested concentrations (p < 0.01 and <0.05, respectively), whereas decreased glutathione reductase activity was found in the groups exposed to ciprofloxacin concentrations of 500 μg L(-1) and 3000 μg L(-1) (p < 0.05). The concentration of thiobarbituric acid-reactive substances was significantly lower (p < 0.01) in all experimental groups exposed to ciprofloxacin. The lowest-observed-effect concentration of ciprofloxacin was 1 μg L(-1) . These results suggest that hatching, early ontogeny, occurrence of morphological anomalies, antioxidant and biotransformation enzyme activity, and lipid peroxidation in fish can be affected by ciprofloxacin. Environ Toxicol Chem 2016;35:1733-1740. © 2015 SETAC.

Conjugated linoleic acid isomers strongly improve the redox status of bovine mammary epithelial cells (BME-UV1)

Some studies have shown the protective effects of conjugated linoleic acid (CLA) isomers against oxidative stress and lipid peroxidation in animal models, but no information is available about CLA and changes in oxidative status of the bovine mammary gland. The objectives of the study were to assess in vitro the effect of CLA on the cellular antioxidant response of bovine mammary cells, to examine whether CLA isomers could play a role in cell protection against the oxidative stress, and to study the molecular mechanism involved. For the study, BME-UV1 cells, a bovine mammary epithelial cell line, were used as the experimental model. The BME-UV1 cells were treated with complete medium containing 50 µM cis-9,trans-11 CLA (c9,t11 CLA), trans-10,cis-12 CLA (t10,c12 CLA), and CLA mixture (1:1, cis-9,trans-11: trans-10,cis-12 CLA). To monitor cellular uptake of CLA isomers, cells and culture medium were collected at 0, 3, and 48h from CLA addition for lipid extraction and fatty acid analyses. To assess the cellular antioxidant response, glutathione (GSH/GSSH), NADPH, and γ-glutamyl-cysteine ligase activity was measured after 48h from addition of CLA. Cytoplasmic superoxide dismutase, glutathione peroxidase, glutathione S-transferase, and glutathione reductase activities and mRNA were also determined. Intracellular reactive oxygen species and thiobarbituric acid reactive substance production were assessed in cells supplemented with CLA isomers. Cell viability after 3h to H2O2 exposure was assessed to evaluate and to compare the potential protection of different CLA isomers against H2O2-induced oxidative stress. Mammary cells readily picked up all CLA isomers, their accumulation was time dependent, and main metabolites at 48h are two 18:3 isomers. The CLA treatment induced an intracellular GSH increase, matched by high concentration of NADPH, and an increase of γ-glutamyl-cysteine ligase activity mainly in cells treated with the t10,c12 CLA isomer. The CLA isomer treatment of bovine mammary cells increased superoxide dismutase, glutathione peroxidase, and glutathione S-transferase activity and decreased glutathione reductase activity, but no changes in gene expression of these antioxidant enzymes were observed. Cells supplemented with CLA isomers showed a reduction in intracellular reactive oxygen species and thiobarbituric acid reactive substance levels. All CLA isomers were able to enhance cell resistance against H2O2-induced oxidative stress. These suggest an antioxidant role of CLA, in particular of t10,c12 CLA, by developing a significantly high redox status in cells.

Protective effect of bixin on carbon tetrachloride-induced hepatotoxicity in rats.

BackgroundThe liver is an important organ for its ability to transform xenobiotics, making the liver tissue a prime target for toxic substances. The carotenoid bixin present in annatto is an antioxidant that can protect cells and tissues against the deleterious effects of free radicals. In this study, we evaluated the protective effect of bixin on liver damage induced by carbon tetrachloride (CCl4) in rats.ResultsThe animals were divided into four groups with six rats in each group. CCl4 (0.125 mL kg-1 body wt.) was injected intraperitoneally, and bixin (5.0 mg kg-1 body wt.) was given by gavage 7 days before the CCl4 injection. Bixin prevented the liver damage caused by CCl4, as noted by the significant decrease in serum aminotransferases release. Bixin protected the liver against the oxidizing effects of CCl4 by preventing a decrease in glutathione reductase activity and the levels of reduced glutathione and NADPH. The peroxidation of membrane lipids and histopathological damage of the liver was significantly prevented by bixin treatment.ConclusionTherefore, we can conclude that the protective effect of bixin against hepatotoxicity induced by CCl4 is related to the antioxidant activity of the compound.

Cationic solid lipid nanoparticles interfere with the activity of antioxidant enzymes in hepatocellular carcinoma cells

Solid lipid nanoparticles (SLN) are colloidal drug and/or gene carriers developed from solid lipids and surfactants that are considered safe. Cationic SLN, usually used for formulating poorly water-soluble drugs and for gene delivery purposes, as positively charged particles may attach to cellular surfaces and be internalized more easily than negatively charged SLN, but they can also cause damage. The main aim of this work was to test a set of cationic SLN and investigate its influence on the amount of reactive oxygen species (ROS), on antioxidant enzymes activities and on possible oxidative damage to membrane lipids in HepG2 cells. The Dichlorofluorescein assay revealed great increase in ROS presence after cell exposure to SLN. While the exposure to SLN increased the activities of superoxide dismutase and glutathione peroxidase it decreased glutathione reductase activity. Although no significant increase in thiobarbituric reactive species was found, a decrease in sulfhydryl groups was detected. These results indicate that cationic SLN caused oxidative stress in HepG2 cells, but under reported exposure conditions HepG2 cells could attenuate the stress and thus the damage to cellular components was minimal.

Goldfish brain and heart are well protected from Ni2 +-induced oxidative stress

After 96h goldfish exposure to 10, 25 or 50mg/L of Ni2+ no Ni accumulation was found in the brain, but lipid peroxide concentration was by 44% elevated in the brain, whereas carbonyl protein content was by 45–45% decreased in the heart. High molecular mass thiol concentration was enhanced by 30% in the heart, while in the brain low molecular mass thiol concentration increased by 28–88%. Superoxide dismutase activity was by 27% and 35% increased in the brain and heart, respectively. Glutathione peroxidase activity was lowered to 38% and 62% of control values in both tissues, whereas catalase activity was increased in the heart by 15–45%, accompanied by 18–29% decreased glutathione reductase activity. The disturbances of free radical processes in the brain and heart might result from Ni-induced injuries to other organs with more prominent changes in the heart, because of close contact of this organ with blood, whereas the blood–brain barrier seems to protect the brain.