Gene expression changes in long-term culture of T-cell clones: genomic effects of chronic antigenic stress in aging and immunosenescence

The adaptive immune response requires waves of T-cell clonal expansion on contact with altered self and contraction after elimination of antigen. In the case of persisting antigen, as occurs for example in cytomegalovirus or Epstein-Barr virus infection, this critical process can become dysregulated and responding T-cells enter into a dysfunctional senescent state. Longitudinal studies suggest that the presence of increased numbers of such T-cells is a poor prognostic factor for survival in the very elderly. Understanding the nature of the defects in these T-cells might facilitate intervention to improve immunity in the elderly. The process of clonal expansion under chronic antigenic stress can be modelled in vitro using continuously cultured T-cells. Here, we have used cDNA array technology to investigate differences in gene expression in a set of five different T-cell clones at early, middle and late passage in culture. Differentially expressed genes were confirmed by real-time polymerase chain reaction, and relationships between these assessed using Ingenuity Systems evidence-based association analysis. Several genes and chemokines related to induction of apoptosis and signal transduction pathways regulated by transforming growth factor beta (TGFbeta), epidermal growth factor (EGF), fos and beta-catenin were altered in late compared to early passage cells. These pathways and affected genes may play a significant role in driving the cellular senescent phenotype and warrant further investigation as potential biomarkers of aging and senescence. These genes may additionally provide targets for intervention.     

Brain antioxidant systems in human methamphetamine users

Animal data suggest that the widely abused psychostimulant methamphetamine can damage brain dopamine neurones by causing dopamine-dependent oxidative stress; however, the relevance to human methamphetamine users is unclear. We measured levels of key antioxidant defences [reduced (GSH) and oxidized (GSSG) glutathione, six major GSH system enzymes, copper-zinc superoxide dismutase (CuZnSOD), uric acid] that are often altered after exposure to oxidative stress, in autopsied brain of human methamphetamine users and matched controls. Changes in the total (n = 20) methamphetamine group were limited to the dopamine-rich caudate (the striatal subdivision with the most severe dopamine loss) in which only activity of CuZnSOD (+ 14%) and GSSG levels (+ 58%) were changed. In the six methamphetamine users with severe (- 72 to - 97%) caudate dopamine loss, caudate CuZnSOD activity (+ 20%) and uric acid levels (+ 63%) were increased with a trend for decreased (- 35%) GSH concentration. Our data suggest that brain levels of many antioxidant systems are preserved in methamphetamine users and that GSH depletion, commonly observed during severe oxidative stress, might occur only with severe dopamine loss. Increased CuZnSOD and uric acid might reflect compensatory responses to oxidative stress. Future studies are necessary to establish whether these changes are associated with oxidative brain damage in human methamphetamine users.     

Assessment of oxidant/antioxidant status in saliva of cell phone users

Hazardous health effects resulting from exposure to radiofrequency electromagnetic radiation (RF-EMR) emitted from cell phones have been reported in the literature. However, the cellular and molecular targets of RF-EMR are still controversial. The aim of this study was to examine the oxidant/antioxidant status in saliva of cell phone users. Saliva samples collected before using a cell phone as well as at the end of 15 and 30?min calls were tested for two commonly used oxidative stress biomarkers: malondialdehyde (MDA) and 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-Oxo-dG). The 8-oxo-dG levels were determined by enzyme-linked immunosorbent (ELISA) competitive assay, while the MDA levels were measured using the OxiSelect MDA adduct ELISA Kit. The antioxidant capacity of the saliva was evaluated using the oxygen radical absorption capacity (ORAC) and the hydroxyl radical averting capacity (HORAC) assays according to the manufacture instructions. The mean 8-oxo-dG and the Bradford protein concentrations (ng/ml and mg/ml, respectively) peaked at 15?min. The levels of HORAC, ORAC and MDA progressively increased with time and reached maximum at 30?min. However, there was no significant effect of talking time on the levels of 8-OxodG and MDA. Similarly, there was no statistically significant effect of talking time on the oxygen and hydroxyl radicals averting capacities, (ORAC) and (HORAC), respectively. These findings suggest that there is no relationship between exposure to radio frequency radiation (RFR) and changes in the salivary oxidant/antioxidant profile.     

Quercetin protects radiation-induced DNA damage and apoptosis in kidney and bladder tissues of rats

Abstract

Ionizing radiation (IR) can induce cell damage and cell death through the reactive oxygen species generated by radiolytic hydrolysis. The present study was aimed to determine the possible protective effects of quercetin, a well-known antioxidant agent, against IR-induced bladder and kidney damage in rats. Sprague-Dawley rats were exposed to 8-Gy whole-abdominal IR and given either vehicle or quercetin (20 mg/kg, ip). Rats were decapitated at either 36 h or 10 days following IR, where quercetin or vehicle injections were repeated once daily, and kidney and bladder samples were obtained for the determination of myeloperoxidase and caspase-3 activities, an index of tissue neutrophil infiltration and apoptosis, respectively. Radiation-induced inflammation was evaluated through tissue cytokine, TNF-α levels. In order to examine oxidative DNA damage, tissue 8-hydroxydeoxyguanosine (8-OHdG) levels were measured. All tissues were also examined microscopically. In the saline-treated irradiation groups, myeloperoxidase and caspase-3 activities, 8-OHdG and TNF-α levels were found to be increased in both tissues (p < 0.05). In the quercetin-treated-IR groups, all these oxidant responses were prevented significantly (p < 0.05). The present data demonstrate that quercetin, through its free radical scavenging and antioxidant properties, attenuates irradiation-induced oxidative organ injury, suggesting that quercetin may have a potential benefit in radiotherapy by minimizing the adverse effects and will improve patient care.     

Genistein protects intervertebral discs from degeneration via Nrf2-mediated antioxidant defense system: An in vitro and in vivo study

Oxidative stress has been reported to be closely associated with the development of intervertebral disc degeneration (IDD). IDD is one of the major causes of low back pain. Genistein (GES), one of the main isoflavones of soybean, has been shown to exert multiple biological functions on different diseases. Here, we tested the therapeutic potential of GES for IDD. In vitro experiments, we confirmed GES was nontoxic to rat nucleus pulposus cells (NPCs) within the concentration of 100 μM. Furthermore, GES was able to suppress apoptosis in tert-butyl hydroperoxide (TBHP)-treated NPCs. In the aspect of extracellular matrix (ECM), GES not only reduced metalloproteinase-13 (MMP-13) and a disintegrin-like and MMP thrombospondin type 1 motif 5 expression, but also increased aggrecan and type II collagen levels. Also, we found GES might rescue TBHP-induced NPCs degeneration by enhancing Nrf2-mediated antioxidant defense system. Silencing Nrf2 partly abolished the protective effects of GES on apoptosis and ECM disruption in TBHP-treated NPCs. Correspondingly, GES ameliorated IDD in a rat model by preserving morphology of degenerative intervertebral discs and promoting Nrf2 expression. To sum up, our study suggests that GES exerts protective effects in NPCs against degeneration and reveals the underlying mechanism of GES on Nrf2 activation in NPCs.     

Comparative study of antioxidant properties and cytoprotective activity of flavonoids

Antioxidant properties and cytoprotective activity of flavonoids (rutin, dihydroquercetin, quercetin, epigallocatechin gallate (EGCG), epicatechin gallate (ECG)) were studied. All these compounds inhibited both NADPH- and CCl₄-dependent microsomal lipid peroxidation, and the catechins were the most effective antioxidants. The I ₅₀ values calculated for these compounds by regression analysis were close to the I ₅₀ value of the standard synthetic antioxidant ionol (2,6-di-tert-butyl-4-methylphenol). The antiradical activity of flavonoids to O ₂ was studied in a model photochemical system. Rate constants of the second order reaction obtained by competitive kinetics suggested flavonoids to be more effective scavengers of oxygen anion-radicals than ascorbic acid. By competitive replacement all flavonoids studied were shown to be chelating agents capable of producing stable complexes with transition metal ions (Fe²⁺, Fe³⁺, Cu²⁺). The flavonoids protected macrophages from asbestos-induced damage, and the protective effect increased in the following series: rutin < dihydroquercetin < quercetin < ECG < EGCG. The cytoprotective effect of flavonoids was in strong positive correlation with their antiradical activity to O ₂ .     

槲皮素体外抗氧化及对小鼠血脂代谢作用的研究

本研究旨在探讨槲皮素体外抗氧化能力以及对高脂日粮小鼠血脂代谢的影响.体外分别测定了槲皮素对DPPH·,·OH和ABTS+·自由基的清除作用.动物实验:将昆明种雄性小鼠32只,随机分为4组,分别饲喂正常、高脂、高脂+0.05g/kg槲皮素、高脂+0.1g/kg槲皮素日粮.9周后测定小鼠肝脏活性氧(Reactive oxygen species,ROS)水平、丙二醛(Malondialdehyde,MDA)含量、抗氧化酶活力及血脂水平.结果表明:槲皮素对DPPH·,·OH和ABTS+·具有较强的清除作用,在一定范围内呈现出明显的剂量增加-效应增强的关系.0.05g/kg槲皮素能显著降低肝脏自由基水平及MDA含量(P＜0.05),增强抗氧化能力(P＜0.05),改善血脂水平(P＜0.05),而0.1g/kg槲皮素效果不显著.结论:0.05g/kg槲皮素可有效提高机体抗氧化能力,缓解高脂膳食造成的氧化应激,改善血脂代谢.     

Elevated temperature effects on the oxidant/antioxidant balance in submerged batch cultures of the filamentous fungus Aspergillus niger B1-D

In the present study the relationship between oxidative stress and elevated culture temperature was examined in an industrially relevant fungal culture, Aspergillus niger B1-D. For the first time, both the intracellular levels of the main stressor species (superoxide radical [O(2) (.-)]) and activities of cellular defensive enzymes (superoxide dismutase [SOD], catalase [CAT], and glutathione peroxide [GPx]) were quantified at varying temperature (25, 30, 35, 40 degrees C) to more fully characterize culture response in different growth phases. Elevated culture temperature led to increased O(2) (.-) levels in various culture phases. In the exponential phase this was due to an enhanced generation of O(2) (.-), whereas in stationary phase a decreased dismutation rate may also have contributed. CAT activities generally increased with culture temperature, whereas GPx activity changed little as temperature rose, indicating that GPx played only a minor role in destroying H(2)O(2) in this A. niger. The combination of elevated temperature (35 degrees C) and increased O(2) supply (50% enrichment) led to decreased levels of O(2) (.-) compared to the cultivation at 35 degrees C gassed with air, probably due to enhanced activity of the alternative fungal respiratory pathway. Our findings indicate that while elevated cultivation temperature does clearly induce oxidative stress events, mechanistically, it does so by a rather more complex route than previous studies indicate. Elevated temperature caused a marked disparity in the activities of SOD and CAT, very distinct from the integrated increase in activity of these enzymes in response to oxidative stress.     

Melatonin ameliorates degenerative alterations caused by age in the rat prostate and mitigates high-fat diet damages

Imbalance of sexual steroids milieu and oxidative stress are often observed during aging and correlated to prostate disorders. Likewise, high-fat intake has been related to prostate damage and tumor development. Melatonin (MLT) is an antioxidant whose secretion decreases in elderly and is also suggested to protect the gland. This study evaluated the impact of a long-term high-fat diet during aging on prostate morphology and antioxidant system of rats and tested the effects of MLT supplementation under these conditions. Male rats were assigned into four groups: control, treated with MLT, high-fat diet and high-fat diet treated with MLT. The high-fat diet was provided from the 24th week of age, MLT from the 48th (100 μg/kg/day) and rats were euthanized at the 62nd week. The high-fat diet increased body weight, retroperitoneal fatness, glycaemia, and circulating estrogen levels. It aggravated the aging effects, leading to epithelial atrophy (∼32% reduction of epithelial height) and collagen fibers increase (83%). MLT alone did not alter biometric and physiological parameters, except for the prostate weight decrease, whereas it alleviated biometric as well as ameliorated acinar atrophy induced by high-lipid intake. Systemic oxidative stress increased, and prostatic glutathione peroxidase activity decreased fivefold with the high-fat diet despite the indole. Regardless of the diet, MLT triggered epithelial desquamation, reduced androgen receptor-positive cells, increased smooth muscle layer thickness (12%), decreased at least 50% corpora amylacea formation, and stimulated prostatic gluthatione-S-transferase activity. In conclusion, MLT partially recovered prostate damage induced by aging and the long-term high-fat diet and ameliorated degenerative prostate alterations.     

Imbalanced oxidant and antioxidant ratio in myotonic dystrophy type 1

Abstract

Myotonic dystrophy type 1 (DM1) is the most common form of muscular dystrophy affecting adults and is due to trinucleotide sequence (CTG) in the 3′ UTR region of DMPK gene located at 19q13.3 chromosome. The pathogenic mechanisms of multisystemic involvement of DM1 are still unclear. The increased levels of reactive oxygen species/free radicals and lipid peroxides and decreased antioxidant levels play an important role in the pathogenesis of DM1. Present study includes 20 DM1 patients and 40 age- and sex-matched controls. Malonilaldehyde (MDA), superoxide dismutase (SOD), glutathione peroxidise (GPX), glutathione-S-transferase (GST), reduced glutathione (GSH), and TAS levels were measured and its association with clinical phenotype were evaluated. Results revealed significantly higher levels of MDA (p = 0.002), SOD (p = 0.006), and TAS p = 0.004) and lower level of GPX (p = 0.003), GST (P < 0.001) and GSH (P = 0.016) in DM1 patients. A significant negative correlation of MDA level with dyspepsia and CK-MB and GST level with serum SCK, CK-MB, and diabetes were observed. However, a significant positive correlation of SOD level with serum CK-MB, CK-MM, and diabetes and negative correlation with facial weakness were noted. Though, GSH level had significant positive correlation with learning and writing disability, speech, and languages disability yet found negative correlation with duration of disease. The GPX and TAS showed no correlation with any clinical findings. Our data further support the pathogenic role of oxidative stress in DM1 of Indian origin and support the opportunity to undertake clinical trials with antioxidants in this disorder.     

Quercetin can be a more reliable treatment for metastatic prostate cancer than the localized disease: An in vitro study

Quercetin is a plant flavonoid that has been recognized to have anti-inflammatory, antioxidant and anti-proliferative activities. This study aims to evaluate the inhibitory effects of quercetin against prostate malignancy in vitro and the underlying resistance mechanism. IC₅₀ values of quercetin were determined by MTT assay. Annexin-V/PI staining was used to measure the rate of apoptosis. DNA cell cycle was analysed by PI staining method. Real-time PCR was performed to assess mRNA levels of OPN isoforms, VEGF isoforms, P53 and KLK2. Migration potential, proliferative capability and nucleus morphology of cells were evaluated by the scratch-wound assay, colony-forming assay and Hoechst staining, respectively. Quercetin significantly increased the apoptosis rate of PC-3 and LNCaP cell lines, arrested the cell cycle at the sub-G1/G1 phase, and reduced the migration potential and colony-forming capability. Moreover, upregulation of apoptosis-related genes and downregulation of genes involved in proliferation and angiogenesis was also observed. Although our results elucidated that quercetin has antitumor effects on PC-3 and LNCaP, for the first time, we showed that quercetin treatment causes alterations in the expression of OPN and VEGF isoforms, which are cancer-promoting modulators through various processes such as angiogenesis and drug-resistance. Prostate malignant cells can dodge the anti-carcinogenic properties of quercetin via modulation of OPN and VEGF isoforms in vitro. Therefore, quercetin acts as a double-edged sword in prostate cancer treatment.     

Vitamin D3 treatment regulates apoptosis,antioxidant defense system,and DNA integrity in the epididymal sperm of an aged rat model

The present study aimed to investigate the effects of vitamin D3 in the epididymal sperm cells of D ‐gal‐induced aged rats. It is well known that during aging sperm quality and quantity declines and leads to age‐related infertility problems in males. The results of the present study showed that there were elevated levels of oxidative stress and poor DNA integrity of sperm of aged rats. The expression of BCL2 also showed a significant decline in the sperm of aged rats, however, the expression of BAX and active caspase‐3 did not show significant change compared with the control group. The treatment of vitamin D3 at lower doses to aged rats showed increased expression of BAX and active caspase‐3 in the sperm, this finding suggests that increased apoptosis may be responsible for removal of poor quality sperm during aging. Vitamin D3 treatment at both doses showed improvement in the oxidative stress and DNA integrity in the sperm of aged rats. We also investigated the expression of AGER, visfatin, and HSPA1A in the epididymal sperm. It has been found that expression of AGER, visfatin, and HSPA1A increased in the sperm aged rats and vitamin D3 treatments at both doses decreased its expression. Thus, it might be suggested that during aging vitamin D3 treatment would be important for managing the sperm quality by regulating the apoptosis, antioxidant system and DNA integrity via modulation of visfatin and HSPA1A.     

Effect of scuba diving on the oxidant/antioxidant status,SIRT1 and SIRT3 expression in recreational divers after a winter nondive period

The aim of this study was to examine the effects of scuba diving on oxidative damage markers in erythrocytes and plasma, antioxidant system in peripheral blood mononuclear cells (PBMCs), as well as sirtuin 1 (SIRT1) and sirtuin 3 (SIRT3) gene expressions in recreational divers after a winter nondive period (at least 5 months). For that purpose, 17 male recreational divers performed an immersion at a depth of 30 m for 30?min. Blood samples were collected immediately before and after diving, 3 and 6?h after diving. Erythrocyte lipid peroxidation measured by thiobarbituric-reactive substances (TBARS) method was significantly increased immediately after diving, but returned to the baseline 6?h after diving, while no significant change was found for plasma TBARS and protein carbonyl derivates in both plasma and erythrocytes. Diving-induced catalase (CAT), superoxide dismutase 2 (SOD2), and consequently total superoxide dismutase (SOD) activities in the PBMC samples (significantly increased immediately after diving, reached the maximum activities 3?h after diving, while 6?h after diving only CAT activity remained significantly increased). No significant change was observed for SOD1 activity and gene expression, as well as SOD2 expression, while CAT and SIRT1 expressions were slightly decreased immediately after diving and 3?h after diving. Interestingly, SIRT3 expression was significantly increased 6?h after diving. In conclusion, after the first dive to 30 m after a nondive season, activation of antioxidant defence was not sufficient to prevent oxidative damage, while SIRT3 upregulation could be a step towards an adaptive response to the diving.     

Effects of erythropoietin and pentoxifylline on the oxidant and antioxidant systems in the experimental short bowel syndrome

In this study, we investigated the effects of erythropoietin (Epo), and pentoxifylline (Ptx) on the oxidant and antioxidant systems in the experimental short bowel syndrome. Spraque-Dawley rats were divided into four groups and all animals underwent 75% small bowel resection. Group E was treated with 500 IU kg(- 1) Epo subcutaneously (s.c.), group P with 50 mg kg(- 1) day(- 1) s.c. Ptx and group E+P with 500 IU kg(- 1) s.c. Epo plus 50 mg kg(- 1) day(- 1) s.c. Ptx for a period of 28 days. In group C, which is the control group, no drug treatment was given. At the end of 28 days the experimented rats were killed and ileum samples excised for biochemical and histopathological testing. Malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels were determined in ileum homogenates. When compared to group C, the MDA and GSH-Px levels were significantly decreased (p < 0.05), but SOD activity was not changed (p > 0.05) in groups P and E+P, whereas both MDA and SOD and also GSH-Px activities were not changed significantly in group E (p > 0.05). The average villous length, crypt depth, muscular thickness and mucosal length were measured in all groups. The average crypt depth and mucosal length were statistically higher in the group P than group C (p < 0.001, p < 0.01, respectively). In addition, the crypt depth was statistically higher in both E and E+P groups as compared to group C (p < 0.001, p < 0.01, respectively). Therefore, our study indicates that Ptx may be more effective than Epo in reducing lipid peroxidation. Moreover, we considered that Ptx may give this protective effect by inhibiting the free oxygen radicals to a greater extent than developing the antioxidant capacity.     

Neuroglobin expression and oxidant/antioxidant balance after graded traumatic brain injury in the rat

Neuroglobin is a neuron-specific hexacoordinated globin capable of binding various ligands, including O₂, NO, and CO, the biological function of which is still uncertain. Various studies seem to indicate that neuroglobin is a neuroprotective agent when overexpressed, acting as a potent inhibitor of oxidative and nitrosative stress. In this study, we evaluated the pathophysiological response of the neuroglobin gene and protein expression in the cerebral tissue of rats sustaining traumatic brain injury of differing severity, while simultaneously measuring the oxidant/antioxidant balance. Two levels of trauma (mild and severe) were induced in anesthetized animals using the weight-drop model of diffuse axonal injury. Rats were then sacrificed at 6, 12, 24, 48, and 120 h after traumatic brain injury, and the gene and protein expression of neuroglobin and the concentrations of malondialdehyde (as a parameter representative of reactive oxygen species-mediated damage), nitrite + nitrate (indicative of NO metabolism), ascorbate, and glutathione (GSH) were determined in the brain tissue. Results indicated that mild traumatic brain injury, although causing a reversible increase in oxidative/nitrosative stress (increase in malondialdehyde and nitrite + nitrate) and an imbalance in antioxidants (decrease in ascorbate and GSH), did not induce any change in neuroglobin. Conversely, severe traumatic brain injury caused an over nine- and a fivefold increase in neuroglobin gene and protein expression, respectively, as well as a remarkable increase in oxidative/nitrosative stress and depletion of antioxidants. The results of this study, showing a lack of effect in mild traumatic brain injury as well as asynchronous time course changes in neuroglobin expression, oxidative/nitrosative stress, and antioxidants in severe traumatic brain injury, do not seem to support the role of neuroglobin as an endogenous neuroprotective antioxidant agent, at least under pathophysiological conditions.     

Cellular senescence and chronological age in various human tissues: A systematic review and meta‐analysis

Senescent cells in tissues and organs are considered to be pivotal to not only the aging process but also the onset of chronic disease. Accumulating evidence from animal experiments indicates that the magnitude of senescence can vary within and between aged tissue samples from the same animal. However, whether this variation in senescence translates across to human tissue samples is unknown. To address this fundamental question, we have conducted a systematic review and meta‐analysis of all available literature investigating the magnitude of senescence and its association with chronological age in human tissue samples. While senescence is higher in aged tissue samples, the magnitude of senescence varies considerably depending upon tissue type, tissue section, and marker used to detect senescence. These findings echo animal experiments demonstrating that senescence levels may vary between organs within the same animal.     

Upregulation of antioxidant and glyoxalase systems mitigates NaCl stress in Brassica juncea by supplementation of zinc and calcium

Possible involvement of calcium (Ca) and zinc (Zn) in mitigation of salt (NaCl) stress-induced oxidative damage in Brassica juncea was investigated. Salt stress (200?mM NaCl) reduced leaf pigment synthesis and some key photosynthetic attributes including stomatal conductance and internal CO₂ concentration. Exogenous application of Ca and Zn resulted in enhanced growth possibly by induction of the antioxidant defense system, resulting in improved redox state thereby favoring growth improvement. Proline accumulation (3.39-fold) was stimulated by exogenous application of Zn and Ca causing improvement in growth through enhancement in relative water content (78.46%) and increased flavonoid accumulation (86.19%). NaCl stress enhanced the hydrogen peroxide (H₂O₂), malondialdehyde and methylglyoxal content by 3-fold, 1.51-fold, and 2.98-fold, respectively, however, supplementation of Ca and Zn individually as well as in combination reduced the accumulation to an appreciable level. Ca and Zn treatment helped Brassica juncea plants to strengthen the antioxidant system and glyoxalase system and also enzymes of ascorbate-glutathione (AsA-Glu) cycle for better protection to membranes from reactive oxygen species. Moreover, Ca and Zn supplementation reduced the salt-induced damage by maintaining Na/K ratio through improved K uptake.     

Effects of selenite and selenate on the antioxidant systems in Senecio scandens L

Abstract

Selenate and selenite are the most prevalent bioavailable selenium (Se) forms and most easily taken up by plants. Some studies indicate that they are differently absorbed and accumulated in plants and that selenium is toxic if accumulated at high concentrations. Toxicity is due to substitution of sulphur by selenium in cysteine and methionine aminoacids with alteration of the tertiary structure and catalytic activity of proteins and with inhibition of enzymes involved in chlorophyll biosynthesis. Moreover, the interaction between Se and thiol groups induces loss of efficiency of plant defence systems and increases the reactive oxygen species (ROS) production thus enhancing the oxidative stress. To further elucidate the role of Se in higher plants, in this study the antioxidative response to the phytotoxicity of selenite and selenate in Senecio scandens L. was evaluated. The data indicate that while selenite induces oxidative stress enhancing ROS production, lipid peroxidation and the oxidised forms of ascorbate and glutathione, selenate does not significantly affect the analysed pathways. This article outlines that the synergistic action of different antioxidant components is necessary to overcome the phytotoxicity of selenium in Senecio.     

Morphological changes and antioxidant defence systems in soybean genotypes as affected by salt stress

Abstract

The present investigation was conducted to evaluate salt tolerance in nine genotypes of soybean (Glycine max L.). Ten-day-old seedlings, grown hydroponically, were treated with 0, 25, 50, 75, 100, 125 and 150 mM NaCl for five days. Growth, lipid peroxidation and antioxidant enzyme activities were evaluated. Growth, measured in terms of length, fresh weight and dry weight of plants, was drastically reduced in PK-416, while there was little effect of NaCl treatment on Pusa-37 genotype of soybean. A high level of lipid peroxidation was observed in PK-416 as indicated by increased level of malondialdehyde. Activities of superoxide dismutase, catalase, ascorbate peroxidase and glutathione reductase were maximum in Pusa-37 where 9-fold, 1-fold, 5-fold and 6-fold increases over control were observed, respectively. The results suggested that PK-416 and Pusa-37 are salt-sensitive and salt-tolerant genotypes of soybean, respectively, and antioxidant defence systems involved in conferring the sensitiveness and tolerance in these genotypes.     

Enhanced thioredoxin,glutathione and Nrf2 antioxidant systems by safflower extract and aceglutamide attenuate cerebral ischaemia/reperfusion injury

A large number of reactive oxygen species (ROS) aggravate cerebral damage after ischaemia/reperfusion (I/R). Glutathione (GSH), thioredoxin (Trx) and nuclear factor (erythroid‐derived 2)‐like 2 (Nrf2) represent three major antioxidant systems and play vital roles in affecting each other in eliminating ROS. Identification of drugs targeting triple antioxidant systems simultaneously is vital for inhibiting oxidative damage after cerebral I/R. This study investigated the protective effect of safflower extract and aceglutamide (SAAG) against cerebral I/R injury through modulating multiple antioxidant systems of GSH, Trx and Nrf2 and identified each role of its component acegluatminde (AG) and safflower extract (SA) on these systems. Safflower extract and aceglutamide and its two components decreased neurological deficit scores, infarction rate, apoptosis and oxidative damage after cerebral I/R while enhanced cell viability, decreased reactive oxygen species and nitric oxide level in H₂O₂‐induced PC12 cell model. Importantly, compared to its two components, SAAG demonstrated more effective enhancement of GSH, Nrf2 and Trx systems and a better protection against cerebral I/R injury. The enhanced antioxidant systems prevented ASK1 activation and suppressed subsequent p38 and JNK cascade‐mediated apoptosis. Moreover, inhibition of Trx and Nrf2 systems by auranofin and ML385 abolished SAAG‐mediated protection, respectively. Thus, enhanced triple systems by SAAG played a better protective role than those by SA or AG via inhibition of ASK1 cascades. This research provided evidence for the necessity of combination drugs from the perspective of multiple antioxidant systems. Furthermore, it also offers references for the study of combination drugs and inspires novel treatments for ischaemic stroke.