Up-regulation Of Antioxidant Activities Research Articles

Nanoparticles of Costus speciosus Ameliorate Diabetes-Induced Structural Changes in Rat Prostate through Mediating the Pro-Inflammatory Cytokines IL 6, IL1β and TNF-α.

Diabetes mellitus is a common global health problem. Among the complications that are frequently associated with DM are the alternation of sexual function and fertility, especially in young men. This study aimed to assess the efficacy of nanoparticles of Costus speciosus (C. speciosus) in preserving the prostatic structure of diabetic rats and to explore the mechanism behind this effect. A model of DM was induced in male albino rats by a single intraperitoneally injection of streptozotocin (STZ, 60 mg/kg body weight). Five groups (n = 10 each) of rats were included in this study: the control, C. speciosus gold nanoparticles-treated (150 mg/kg body weight through gastric intubation for 30 days), untreated diabetic, metformin-treated diabetic (500 mg/kg/day gastric intubation for 30 days) and the C. speciosus-treated diabetic group. The blood glucose, insulin and testosterone levels as well as oxidants/antioxidants status were assessed in the serum. Gene expression of proinflammatory cytokines TNF-α, IL1β and IL-6 were assessed in the prostate homogenate. At the end of the experiment, the rats were sacrificed and the prostate was dissected out and prepared for histopathological and immunohistochemistry study using Ki67 and Bcl-2. C. Speciosus nanoparticles significantly decreased (p = 0.03) the blood glucose level while significantly increasing insulin (p = 0.01) and testosterone (p = 0.04) levels compared to the untreated diabetic rats. Oxidants/antioxidants status was markedly improved after administration of C. speciosus. Prostatic expression of the mRNA of pro-inflammatory cytokines IL-6, IL1β and TNF-α was down-regulated in metformin- and C. speciosus-treated rats. The histological structure of the ventral prostate was preserved in metformin- and C. speciosus-treated diabetic rats with a significantly thicker epithelial cell layer and significant increase immunoexpression in Bcl-2 and Ki67. In conclusion, the protective effect induced by C. speciosus nanoparticles on the prostate of diabetic rats might be directly mediated through the down-regulation of inflammatory cytokines and the up-regulation of antioxidant activity and indirectly mediated through the anti-hyperglycemic effect through enhancing insulin secretion.

Effect of non-thermal plasma (NTP) on common sunflower (Helianthus annus L.) seed growth via upregulation of antioxidant activity and energy metabolism-related gene expression

Effect of non-thermal plasma (NTP) on common sunflower (Helianthus annus L.) seed growth via upregulation of antioxidant activity and energy metabolism-related gene expression

Strenuous Acute Exercise Induces Slow and Fast Twitch-Dependent NADPH Oxidase Expression in Rat Skeletal Muscle.

The enzymatic complex Nicotinamide Adenine Dinucleotide Phosphate (NADPH) oxidase (NOx) may be the principal source of reactive oxygen species (ROS). The NOX2 and NOX4 isoforms are tissue-dependent and are differentially expressed in slow-twitch fibers (type I fibers) and fast-twitch fibers (type II fibers) of skeletal muscle, making them different markers of ROS metabolism induced by physical exercise. The aim of this study was to investigate NOx signaling, as a non-adaptive and non-cumulative response, in the predominant fiber types of rat skeletal muscles 24 h after one strenuous treadmill exercise session. The levels of mRNA, reduced glycogen, thiol content, NOx, superoxide dismutase, catalase, glutathione peroxidase activity, and PPARGC1α and SLC2A4 gene expression were measured in the white gastrocnemius (WG) portion, the red gastrocnemius (RG) portion, and the soleus muscle (SOL). NOx activity showed higher values in the SOL muscle compared to the RG and WG portions. The same was true of the NOX2 and NOX4 mRNA levels, antioxidant enzymatic activities, glycogen content. Twenty-four hours after the strenuous exercise session, NOx expression increased in slow-twitch oxidative fibers. The acute strenuous exercise condition showed an attenuation of oxidative stress and an upregulation of antioxidant activity through PPARGC1α gene activity, antioxidant defense adaptations, and differential gene expression according to the predominant fiber type. The most prominent location of detoxification (indicated by NOX4 activation) in the slow-twitch oxidative SOL muscle was the mitochondria, while the fast-twitch oxidative RG portion showed a more cytosolic location. Glycolytic metabolism in the WG portion suggested possible NOX2/NOX4 non-regulation, indicating other possible ROS regulation pathways.

Heat stress hardening of oriental armyworms is induced by a transient elevation of reactive oxygen species during sublethal stress.

Pre-exposure to mild heat stress enhances the thermotolerance of insects. Stress hardening is a beneficial physiological plasticity, but the mechanism underlying it remains elusive. Here we report that reactive oxygen species (ROS) concentrations were quickly and transiently elevated in the armyworms, Mythimna separata, by exposing them to 40°C, but not other tested temperatures. Larvae exposed to 40°C had subsequently elevated antioxidant activity and the highest survival of all tested heating conditions. The elevation of ROS after lethal heating at 44°C for 1 h was approximately twofold compared to heating at 40°C. Injection of an optimal amount of hydrogen peroxide (H2 O2 ) similarly caused sequential elevation of ROS and antioxidant activity in the test larval hemolymph, which led to significantly enhanced survival after lethal heat stress. The H2 O2 -induced thermotolerance was abolished by coinjection of potent antioxidants such as ascorbic acid or N-acetylcysteine. Both preheating at 40°C and H2 O2 injection enhanced expression of genes encoding superoxide dismutase 1, catalase, and heat shock protein 70 in the fat body of test larvae, indicating the adequate heat stress induced a transient elevation of ROS, followed by upregulation of antioxidant activity. We infer that thermal stress hardening is induced by a small timely ROS elevation that triggers a reduction-oxidation signaling mechanism.

Lifespan extension in Caenorhabditis elegans insulin/IGF-1 signalling mutants is supported by non-vertebrate physiological traits

The insulin/IGF-1 signalling (IIS) pathway connects nutrient levels to metabolism, growth and lifespan in eukaryotes ranging from yeasts to humans, including nematodes such as the genetic model organismCaenorhabditis elegans. The link between ageing and the IIS pathway has been thoroughly studied inC. elegans; upon reduced IIS signalling, a genetic survival program is activated resulting in a drastic lifespan extension. One of the components of this program is the upregulation of antioxidant activity but experiments failed to show a clear causal relation to longevity. However, oxidative damage, such as protein carbonyls, accumulates at a slower pace in long-livedC. elegansmutants with reduced IIS. This is probably not achieved by increased macroautophagy, a process that sequesters cellular components to be eliminated as protein turnover rates are slowed down in IIS mutants. The IIS mutantdaf-2, bearing a mutation in the insulin/IGF-1 receptor, recapitulates the dauer survival program, including accumulation of fat and glycogen. Fat can be converted into glucose and glycogenviathe glyoxylate shunt, a pathway absent in vertebrates. These carbohydrates can be used as substrates for trehalose synthesis, also absent in mammals. Trehalose, a non-reducing homodimer of glucose, stabilises intracellular components and is responsible for almost half of the lifespan extension in IIS mutants. Hence, the molecular mechanisms by which lifespan is extended under reduced IIS may differ substantially between phyla that have an active glyoxylate cycle and trehalose synthesis, such as ecdysozoans and fungi, and vertebrate species such as mammals.

Protective effects of PGC-1α via the mitochondrial pathway in rat brains after intracerebral hemorrhage

Peroxisome-proliferator-activated receptor co-activator-1α (PGC-1α) is a transcriptional co-activator that coordinately regulates genes required for mitochondrial biogenesis, which stimulates mitochondrial activity. It is also a major factor in the up-regulation of antioxidant activities that are a response to oxidative stress. However, the role of PGC-1α after intracerebral hemorrhage (ICH) has not been studied. The purpose of the present work was to investigate the effects and mechanism of PGC-1α after ICH in the brain.Brain injury was induced by injecting autologous arterial blood (50μL) into the rat brain. PGC-1α siRNAs were injected into rat brains 24h prior to ICH. Then, 72h after ICH, brains were collected for investigation. Post-assessment included western blot analysis, RT-PCR assay, neurobehavioral function testing, measurement of brain water content, high-performance liquid chromatography (HPLC), and projection electron microscopy on ICH rat models. The concentration of PGC-1α was higher in the ipsilateral striatum after ICH, peaking around 72h after ICH. The expression of NRF-1, TFAM, SOD2, UCP2, mitochondrial DNA, ATP concentration, mitochondrial quantity, and brain water content were increased 72h after ICH. However, the neurological score was decreased 72h after ICH. Treatment with PGC-1α siRNAs significantly decreased the neurological score, ATP concentration, number of mitochondria, expression of NRF-1, TFAM, SOD2, UCP2, and mitochondrial DNA, and increased brain water content and formation of mitochondrial myelin layer structures. In conclusion, our data suggest that PGC-1α protects rat brains via a mitochondrial pathway following ICH. Key words: PGC-1α intracerebral hemorrhage(ICH); mitochondrial; neuroprotection.

The Effect of Dietary n6:n3 Polyunsaturated Fatty Acid Ratio on Chronic Reflux Esophagitis in Rats

Introduction: Reflux esophagitis (RE) is one of the typical lesions of gastroesophageal reflux disease (GERD). The incidence of GERD is thought related to high fat diet, while the ratio of dietary n6: n3 polyunsaturated fatty acid (PUFAs) is believed to play a role in the regulation of the inflammatory process. This study was aimed to investigate the effect of dietary n6: n3 PUFAs ratio on chronic RE in a rat model and the relationship with lipid peroxidation. Methods: Forty rats were randomly divided into 4 groups according to the n-6: n-3 PUFAs ratios in feed, including 1:1.5,10:1, 5:1 and pure n-6 PUFAs groups, and a sham operation group (10 rats, which were fed with pure n-6 PUFAs) was set up as blank control. Rat RE model (Pyloric Nylon Loop-induced Chronic Acid Reflux Esophagitis) was established by pyloric clip and section ligation. After 14 days treatment, pathological changes of the esophagus were determined, and the expression of IL-1β, IL-8, TNFα protein and mRNA in esophageal tissue homogenate were evaluated by Western blot and RT-PCR, respectively, while the MDA and SOD levels were evaluated by ELISA, respectively. Results: The food intake and body weights in the rats showed no significant difference before operation (P>0.05), while those were reduced in all groups except sham group in postoperative d7 (P<0.05) and were recovered in d14, and no intergroup differences were found (P>0.05). In PUFA1:1.5, PUFA5:1, PUFA10:1, n-6 PUFA groups and sham operation group, the postoperative d14 survival rates were 70%, 60%, 80%, 70% and 100%, respectively (P=0.306). The degree of esophagitis was lower in PUFA1:1.5 group when compared to that in the other model groups (P<0.05), but no significant difference was found among PUFA5:1, PUFA10:1 and n-6 PUFA groups(P>0.05). The protein and mRNA expression of IL-1β, IL-8 and TNFα, and the MDA levels were increased in all model groups when compared to that in sham group (P<0.05), which showed a rising tendency from PUFA1:1.5, PUFA5:1, PUFA10:1 groups to n-6 PUFA group. The SOD levels were decreased in all model groups when compared to that in sham group (P<0.05), which showed a reducing tendency from PUFA1:1.5, PUFA5:1, PUFA10:1 groups to n-6 PUFA group. Conclusion: The results indicate that the reflux related esophageal mucosal damage could be lightened by adding more n-3 PUFAs in diet, which was associated with an up-regulation of antioxidant activity and a down-regulation of lipid peroxidation in esophageal epithelium. Dietary n-6/n-3 PUFAs ratio reduction may be a beneficial strategy for gastroesophageal reflux disease management.

Artemisia capillaris extract protects against bile duct ligation-induced liver fibrosis in rats

Artemisia capillaris has been widely used as a traditional herbal medicine in the treatment of liver diseases. However, no previous study has investigated whether A. capillaries alone is effective in treating pathological conditions associated with cholestatic liver injury. In the present study, we evaluated the anti-hepatofibrotic effects of A. capillaris (aqueous extract, WAC) in a bile duct ligation (BDL)-induced cholestatic fibrosis model. After BDL, rats were given WAC (25 or 50 mg/kg) or urosodeoxycholic acid (UDCA, 25 mg/kg) orally for 2 weeks (once per day). The serum cholestatic markers, malondialdehyde, and liver hydroxyproline levels were drastically increased in the BDL group, while administering WAC significantly reduced these alterations. Administering WAC also restored the BDL-induced depletion of glutathione content and glutathione peroxidase activity. Cholestatic liver injury and collagen deposition were markedly attenuated by WAC treatment, and these changes were paralleled by the significantly suppressed expression of fibrogenic factors, including hepatic alpha-smooth muscle actin (α-SMA), platelet-derived growth factor (PDGF), and transforming growth factor beta (TGF-β). The beneficial effects of WAC administration are associated with antifibrotic properties via both upregulation of antioxidant activities and downregulation of ECM protein production in the rat BDL model.

The expression of PGC-1α in the mice brain after traumatic brain injury

Background: Peroxisome proliferator activated receptor γ co-activator-1α (PGC-1α) is a transcriptional co-activator that co-ordinately regulates genes required for mitochondrial biogenesis and is a key contributor to the up-regulation of antioxidant activities in response to oxidative stress. The expression pattern of PGC-1α after traumatic brain injury (TBI) has not been studied.Materials and methods: Ninety male ICR mice (28–32 g) were randomly assigned to six groups: sham, 3, 6, 12, 24 and 48 hours after TBI. PGC-1α mRNA levels in mice brain were detected by reverse-transcriptase polymerase chain reaction and its nuclear protein levels by Western blot from 3–48 hours after TBI. PGC-1α distribution in the cerebral cortex after TBI was investigated by immunohistochemistry.Main outcomes and results: The PGC-1α mRNA level significantly increased from 3 hours after TBI, peaked at 6 hours and gradually decreased from 12 to 48 hours. The nuclear PGC-1α protein level increased from 6 to 24 hours after TBI and decreased at 48 hours after TBI. Increased PGC-1α immunostaining was detected in the neurons of the cerebral cortex at 12 hours after TBI.Conclusion: PGC-1α may play an important role in the brain after TBI.

An Extract ofPhellinus linteusGrown on Germinated Brown Rice Inhibits Inflammation Markers in RAW264.7 Macrophages by Suppressing Inflammatory Cytokines, Chemokines, and Mediators and Up-Regulating Antioxidant Activity

The immunomodulatory activity of an organic extract of Phellinus linteus grown on slightly germinated brown rice (PBR) was previously demonstrated. Here, we investigated the possible anti-inflammatory activity of the PBR extract by analyzing its effect on the expression of macrophage-derived cytokines, chemokines, and mediator genes that participate in immune and inflammatory responses and diseases. The extract profoundly inhibited the induction of cytokines and chemokines, including tumor necrosis factor-α, chemokine (C-X-C motif) ligand-10, granulocyte-macrophage colony-stimulating factor, and interleukin-6, in lipopolysaccharide (LPS)-stimulated RAW264.7 mouse macrophage cells. It also greatly inhibited LPS-stimulated production of nitric oxide (NO) and prostaglandin E(2) in RAW264.7 cells by suppressing the expression of inducible NO synthase and cyclooxygenase-2. PBR extract inhibited NO production with a twofold lower half-maximal inhibitory concentration value than P. linteus extract. To elucidate the underlying mechanism of action, we examined the effect of the PBR extract on the LPS-induced phosphorylation of mitogen-activated protein kinases (MAPKs) in RAW264.7 cells. PBR extract greatly inhibited extracellular signal-regulated kinase and c-Jun N-terminal kinase phosphorylation and slightly inhibited p38 MAPK phosphorylation. It also significantly increased intracellular glutathione peroxidase activity and heme oxygenase-1 protein expression. Thus, the PBR extract has anti-inflammatory activity in LPS-stimulated RAW264.7 cells by virtue of its ability to suppress the production of inflammatory cytokines and chemokines via inhibition of MAPK activation and up-regulation of antioxidant activities.

The influence of α-amanitin on the NaCl-induced up-regulation of antioxidant enzyme activity in cotton callus tissue

Liquid suspensions of cotton callus tissue from a NaCl-sensitive cell line and a NaCl-tolerant cell line were subjected to the following treatments: (a) 0 and 150 mM NaCl, respectively (controls); (b) 75 and 250 mM NaCl, respectively; (c) 100 ng ml-1 α-amanitin; or (d) pretreatment for 2 h with 100 ng ml-1 α-amanitin followed by the respective NaCl treatments. The callus tissue was harvested at 0, 0.5, 1, 2, 4, and 8 h and analyzed for antioxidant enzyme activity. In the NaCl-tolerant callus, the 250 mM NaCl treatment resulted in transient 2- to 4-fold increases above the control levels in the activities of ascorbate peroxidase, catalase, glutathione reductase, and peroxidase within 1 h after treatment, while superoxide dismutase activity increased 4-fold within 4 h. This rapid increase suggests that the up-regulation of antioxidant capacity is an early response to NaCl stress and perhaps provides protection against oxidative damage until other acclimating mechanisms can be invoked. In the control callus, peroxidase activity remained unchanged, and significant increases in the other enzymes were not observed until 8 h after treatment with 75mM NaCl. Pre-treatment with α-amanitin prior to the NaCl treatment completely inhibited the NaCl-induced increase in the activities of all five enzymes in both cell lines. This data supports the conclusion that the NaCl-induced up-regulation of antioxidant enzyme activity in cotton callus tissue is transcriptionally regulated, proceeding via a de novo synthesis of poly(A)+RNA and is not due to the translation of existing transcripts or the mobilization of existing enzyme pools. In addition, the results suggest that it is not only the up-regulation of anti-oxidant activity that bestows a degree of tolerance to environmental stress, but also the speed with which this response occurs.