Expression Of Glutathione Reductase Research Articles

GR1-like gene expression in Lycium chinense was regulated by cadmium-induced endogenous jasmonic acids accumulation.

The G1-like gene from the Lycium chinensewas cloned and transferred into N. tabacum. Evidence showed that endogenous JA accumulation was crucial to LcGRgene expression in cadmium-stressed L. chinense. Glutathione reductase (GR) plays a vital role in glutathione-ascorbate metabolism and is a key enzyme in maintaining the redox state in plants. Jasmonic acids (JA) are important hormones regulating protective responses against bacteria and mechanic damage in plants. At present, the relationship between the endogenous JA accumulation, the glutathione (GSH) content and GR gene expression in plants under cadmium (Cd) stress has not been elucidated. This study primarily aims to explore their interconnected relations. First, we isolated theGR1-like gene fromLycium chinense (LcGR). Real-time PCR showed that gene LcGR and allene oxide cyclase (LcAOC) (a JA synthesis gene) expression in L. chinense plants was significantly enhanced by CdCl2 and reduced by CdCl2 cotreatment with 12,13-epoxy-octadecenoic acid (EOA), a JA synthesis inhibitor. Meanwhile, the JA content in plants strongly increased under Cd stress and decreased under Cd+EOA treatment, which was in accordance with expression pattern of LcAOC. The function of gene LcGR was confirmed in vitro with E. coli expression system. The subcellular localization in chloroplasts of LcGR gene was proved in Nicotiana tabacum leaves with transient transfection system of Agrobacterium tumefaciens. Furthermore, the overexpression of gene LcGR in the transgenic tabacum led to great Cd-tolerance and higher GSH accumulation. Overall, the results showed that the endogenous JA accumulation in Cd-stressed plants affects the GR expression which is crucial to the GSH accumulation and GSH-dependent tolerance to cadmium in LcGR transformants.

MicroRNA-144 modulates oxidative stress tolerance in SH-SY5Y cells by regulating nuclear factor erythroid 2-related factor 2-glutathione axis.

Genome-wide analysis of miRNA expression has revealed increased levels of miR-144 in the brains of Alzheimer's disease (AD) patients. Nuclear factor erythroid 2-related factor 2 (NRF2), a potential target of miR-144, is a central regulator of antioxidant response, and plays an important role in glutathione (GSH) biosynthesis and recycling. In this study, miR-144 mimic was used to over express miR-144. Aβ (1-42) was used to induce oxidative stress in SH-SY5Y cells. Cell viability and intracellular reactive oxygen species (ROS) were assessed to identify the effects of miR-144 on oxidative stress status. GSH and glutathion peroxidase (GPX) activities were detected to reveal the effect of miR-144 on GSH accumulation. To understand the effects of miR-144 on GSH biosynthesis and recycling, intracellular GPX1, glutamate-cysteine ligase catalytic subunit (GCLC), glutamate-cysteine ligase modifier subunit (GCLM), glutathione reductase (GR), and NRF2 expression were detected by western blot and Real-time PCR. In oxidative stress conditions, miR-144 increased the intracellular accumulation of ROS, reduced cell viability, reduced the activities of GSH and antioxidant enzymes, GPX1, and decreased the expression of GCLC, GCLM, GR and NRF2. In conclusion, miR-144 modulates oxidative stress tolerance by regulating NRF2 expression and GSH generation, which may contribute to the pathogenesis of AD.

Alleviative effects from boswellic acid on acetaminophen-induced hepatic injury - Corrected and republished from: Biomedicine (Taipei). 2016 Jun; 6 (2): 9. doi: 10.7603/s40681-016-0009-1PMCID: PMC4864770.

Protective effects of boswellic acid (BA) against acetaminophen (APAP)-induced hepatotoxicity in Balb/ cA mice were examined. BA, at 0.05 or 0.1%, was supplied for 4 weeks. Acute liver injury was induced by APAP treatment. Results showed that BA intake increased hepatic BA bioavailability. APAP treatment decreased glutathione (GSH) level, increased reactive oxygen species (ROS) and oxidized glutathione (GSSG) production; and lowered activity and protein expression of glutathione reductase (GR) and heme oxygenase (HO)-1 in liver. BA intake at both doses alleviated subsequent APAP-induced oxidative stress by retaining GSH content, decreasing ROS and GSSG formations, reserving activity and expression of GR and HO-1 in liver, and lowering hepatic cytochrome P450 2E1 activity and expression. APAP treatment enhanced hepatic levels of interleukin-6, tumor necrosis factor-alpha and monocyte chemoattractant protein-1. BA pre-intake diminished APAP-induced release of those inflammatory cytokines and chemokines. APAP up-regulated hepatic protein expression of toll-like receptor (TLR)-3, TLR-4, MyD88, nuclear factor kappa B (NF-κB) p50, NF-κB p65 and JNK. BA pre-intake at both doses suppressed the expression of NF-κB p65 and p-JNK, and only at 0.1% down-regulated hepatic TLR-3, TLR-4 and MyD88 expression. APAP led to obvious foci of inflammatory cell infiltration in liver, determined by H&E stain. BA intake at both doses attenuated hepatic inflammatory infiltration. These findings support that boswellic acid is a potent hepato-protective agent.

Profiling of antioxidative enzyme expression induced by various food components using targeted proteome analysis.

A method was developed for targeted proteome analysis of the expression profile of a set of antioxidative enzymes in rat macrophages and applied to screen the antioxidative potential of several food components/foods. Expression profiles of heme oxygenase 1, peroxiredoxin 1, thioredoxin reductase 1, glutathione reductase, glutathione-S transferase P1, and superoxide dismutase 1 were analyzed by nanoLC-MS/MS in selected scheduled reaction monitoring (sSRM) mode monitoring two to three peptides per protein and three transitions per peptide. Relative quantification was performed by metabolic labeling. The validated method was used to profile the activity of capsaicin, carnosol, diallyl trisulfide, maslinic acid, quercetin, sulforaphane, cinnamaldehyde and coffee extract to modulate the expression levels of antioxidative enzymes. Carnosol and sulforaphane most effectively induced protein expression, leading to upregulation of at least five out of the six antioxidative enzymes by a maximum factor of 22.80 ± 6.71 (heme oxygenase 1 by carnosol). Heme oxygenase 1 was most susceptible to nutritive modulation, whereas glutathione reductase expression rates were hardly affected. Targeted mass proteome analysis allows comprehensive evaluation of antioxidative effects by food ingredients. Simultaneous expression analysis of a set of proteins provided valuable insights how various enzymes were differently affected by food components.

Responses of pomegranate cultivars to severe water stress and recovery: changes on antioxidant enzyme activities, gene expression patterns and water stress responsive metabolites.

The biochemical and molecular responses of five commercially well-known pomegranate cultivars to severe water stress were studied. The cultivars were subjected to 14-day water stress by withholding irrigation, followed by re-watering for 7days. Results showed clear differences in metabolites contents and activities of antioxidant enzymes among various pomegranate cultivars during severe water stress and recovery. According to our results, increased accumulation of proline in pomegranate was not related to osmotic adjustment during severe water stress. Except for 'Ghojagh', leaves grown under severe water stress conditions showed symptoms of oxidative stress such as reduced chlorophyll concentration. The improved performance of 'Ghojagh' under drought stress may be associated with an efficient osmotic adjustment. The up- or down regulated expression of cytosolic glutathione reductase (cytosolic GR) and glutathione peroxidase were observed under drought conditions. Moreover, the suppressed expression of cytosolic GR was also noted. Comparatively, 'Rabab' exhibited higher antioxidant capacity and an efficient ROS-scavenging mechanism under drought stress. Lower levels of membrane lipid peroxidation in 'Ghojagh' and 'Rabab' under drought stress and the marked reduction of malondialdehyde concentration after re-watering represents that these cultivars have a good tolerance to drought stress. As a first step towards the study of the biochemical and molecular responses of pomegranate plants to water stress, this research provides new information into the mechanisms of drought tolerance in the plants.

Transcriptomic responses of selected genes against chromium stress in Arundo donax L.

ABSTRACTRecently, giant reed (Arundo donax L.) has emerged as a useful bioresource capable of coping under harsh abiotic stress conditions produced by exposure to heavy metals, drought and salinity as evidenced by significant biomass production. The current study was undertaken to determine the expression of critical genes involved in resisting oxidative stress and maintaining normal cellular functions. The critical genes examined included glutathione reductase (GR) that prevents oxidative damage of membranes, carotenoid hydroxylase (CR), transcription factor (bHLH) and amidase involved in biosynthesis of indole-3-acetic acid following exposure to chromium (Cr) stress at concentrations of 0, 33.5, 67, 133 or 268 mg/L in giant reed. The S19 gene was used as internal control. It was not possible to extract RNA from severely stressed giant plant leaves at 133 and 268 mg/L Cr. Therefore, this investigation focused on gene expression in the presence of at 0, 33.5 or 67 mg/L Cr. Following Cr-mediated stress, gene expression of GR and CR was increased at 33.5 mg/L but reduced at 67 mg/L. The transcription factor, bHLH, gene expression remained unchanged. Amidase gene expression was elevated at 67 mg/L Cr. Data suggested that over expression of amidase and GR genes at high Cr exposure might increase growth and biomass of giant reed as well as enhance tolerance. These results indicated that giant reed tolerated the presence of Cr stress due to over expression of amidase and GR genes. It would appear that giant reed may serve a beneficial role for phytoremediation of Cr contaminated wastewater and soils at concentrations below 100 mg/kg.

Retraction Note to: Coordinated response of sulfate transport, cysteine biosynthesis, and glutathione-mediated antioxidant defense in lentil (Lens culinaris Medik.) genotypes exposed to arsenic.

Response of sulfate transporters, thiol metabolism, and antioxidant defense system was studied in roots of two lentil (Lens culinaris Medik.) genotypes grown in arsenic (10, 25, and 40 μM As(V))-supplemented nutrient solution, and significant changes compared to control (0 μM As(V)) were observed mainly at 25 and 40 μM. In L 414, high glutathione (GSH) redox (0.8-0.9) was maintained with elevated thiol synthesis, powered by transcriptional up-regulation of LcSultr1;1 and LcSultr1;2 sulfate transporters and significant induction of LcSAT1;1 and LcSAT1;2 (serine acetyltransferase), OAS-TL (O-acetylserine(thiol)-lyase), γ-ECS (γ-glutamylcysteine synthetase), and PCS (phytochelatin synthase) genes predominantly within 12-24 h of As exposure at 25 μM and within 6-12 h at 40 μM. This thiolic potency in L 414 roots was effectively complemented by up-regulation of gene expressions and consequent enhanced activities of superoxide dismutase, ascorbate peroxidase (APX), dehydroascorbate reductase, glutathione reductase (GR), and glutathione-S-transferase (GST) isoforms at 25 and 40 μMAs, efficiently scavenging excess reactive oxygen species to prevent onset of As-induced oxidative stress and consequent inhibition of root growth in L 414. In contrast, down-regulation of vital sulfate-uptake transporters as well as entire thiol-metabolizing system and considerably low APX, GST, and GR expressions in DPL 59 not only resulted in reduced GSH redox but also led to over-accumulation of H2O2. This triggered membrane lipid peroxidations as the marks of As-induced oxidative damage. Results indicated coordinated response of thiol-metabolism and antioxidant defense in conferring As-tolerance in lentil, and GSH is the key point in this cascade.

Induction of Nrf2-mediated phase II detoxifying/antioxidant enzymes in vitro by chitosan-caffeic acid against hydrogen peroxide-induced hepatotoxicity through JNK/ERK pathway.

Chemical modification of chitosan is a promising method for the improvement of biological activity. In this study, chitosan-caffeic acid (CCA) was prepared and its in vitro hepatoprotective ability against hydrogen peroxide-induced hepatic damage in liver cells was evaluated. Treatment with CCA (50-400µg/mL) did not show cytotoxicity and also significantly (p<0.05) recovered cell viability against 650µM hydrogen peroxide-induced hepatotoxicity. CCA treatment attenuated reactive oxygen species generation and lipid peroxidation in addition to increasing cellular glutathione level in cultured hepatocytes. To validate the underlying mechanism, antioxidant and phase II detoxifying enzyme expressions, which are mediated by NF-E2-related factor 2 (Nrf2) activation, were analyzed and CCA treatment was found to increase the expression of superoxide dismutase-1 (SOD-1), glutathione reductase (GR), heme oxygenase-1 (HO-1), and NAD(P)H:quinine oxidoreductase 1 (NQO1). CCA treatment resulted in increased Nrf2 nuclear translocation. The phosphorylation of extracellular regulated kinase (ERK), c-Jun NH2-terminal kinase (JNK), and p38 mitogen-activated protein kinase (MAPK) by CCA treatment contributed to Nrf2 activation. Pharmacological blockade of ERK, JNK, and p38 MAPK revealed that SP600125 (JNK inhibitor) and PD98059 (ERK inhibitor) treatment reduced Nrf2 translocation into the nucleus while SB203580 (p38 inhibitor) exhibited weak inhibition. Collectively, CCA protects liver cells against hydrogen peroxide-induced injury and this ability is attributed to the induction of antioxidants and phase II detoxifying enzymes that are mediated by Nrf2 translocation via JNK/ERK signaling.

Effects of exogenous spermidine on antioxidant system of tomato seedlings exposed to high temperature stress

The effects of foliar spraying with spermidine (Spd) on antioxidant system in tomato (Lycopersicon esculentum Mill.) seedlings were investigated under high temperature stress. The high temperature stress significantly inhibited plant growth and reduced chlorophyll (Chl) content. Application of exogenous 1 mM Spd alleviated the inhibition of growth induced by the high temperature stress. Malondialdehyde (MDA), hydrogen peroxide (H2O2) content and superoxide anion (O2) generation rate were significantly increased by the high temperature stress, but Spd significantly reduced the accumulation of reactive oxygen species (ROS) and MDA content under the stress. The high temperature stress significantly decreased glutathione (GSH) content and activities of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), ascorbate peroxidase (APX), glutathione reductase (GR), monodehydroascorbate reductase (MDHAR) and dehydroascorbate reductase (DHAR), but increased contents of dehydroascorbic acid (DHA), ascorbic acid (AsA), and oxidized glutathione (GSSG) in tomato leaves. However, Spd significantly increased the activities of antioxidant enzymes, levels of antioxidants and endogenous polyamines in tomato leaves under the high temperature stress. In addition, to varying degrees, Spd regulated expression of MnSOD, POD, APX2, APX6, GR, MDHAR, DHAR1, and DHAR2 genes in tomato leaves exposed to the high temperature stress. These results suggest that Spd could change endogenous polyamine levels and alleviate the damage by oxidative stress enhancing the non-enzymatic and enzymatic antioxidant system and the related gene expression.

Arginase activity in Arabidopsis thaliana infected with Heterodera schachtii

The activity of arginase (ARGAH), which results in ornithine and urea production, is important for nitrogen metabolism in all organisms as well as for defence responses. The second‐stage juveniles of the cyst‐forming nematode Heterodera schachtii penetrate roots and induce the formation of a permanent feeding site. To determine whether infection with H. schachtii causes the induction of arginase, the expression was studied in Arabidopsis roots and shoots at the day of inoculation and at 3, 7 and 15 days post‐inoculation (dpi). Parasite infection caused a strong decrease of root arginase activity and ARGAH1 gene expression, which persisted over the entire examination period. In shoots, the mRNA expression of ARGAH2 increased at 3 and 7 dpi, but the enzymatic activity was significantly enhanced only at 3 dpi. Thus, while arginase down‐regulation occurs in roots, which is apparently due to the presence of nematode effectors, in shoots the activity is only transiently up‐regulated despite persistently high gene expression. As oxidative stress is possible during nematode infection, the activity and gene expression of glutathione reductase, a marker of the redox equilibrium, were estimated and found to be significantly enhanced at 7 dpi in shoots of infected plants. The level of proline, an amino acid known for its ability to scavenge free radicals, was increased 60‐fold. The results suggest that the disruption of redox homeostasis, as reflected by increased proline level and glutathione reductase expression and activity, accompanies changes in arginine metabolism in the shoots, indicating systemic changes induced by nematode infection.

Regulation of Plant Growth, Photosynthesis, Antioxidation and Osmosis by an Arbuscular Mycorrhizal Fungus in Watermelon Seedlings under Well-Watered and Drought Conditions.

Drought stress has become an increasingly serious environmental issue that influences the growth and production of watermelon. Previous studies found that arbuscular mycorrhizal (AM) colonization improved the fruit yield and water use efficiency (WUE) of watermelon grown under water stress; however, the exact mechanisms remain unknown. In this study, the effects of Glomus versiforme symbiosis on the growth, physio-biochemical attributes, and stress-responsive gene expressions of watermelon seedlings grown under well-watered and drought conditions were investigated. The results showed that AM colonization did not significantly influence the shoot growth of watermelon seedlings under well-watered conditions but did promote root development irrespective of water treatment. Drought stress decreased the leaf relative water content and chlorophyll concentration, but to a lesser extent in the AM plants. Compared with the non-mycorrhizal seedlings, mycorrhizal plants had higher non-photochemical quenching values, which reduced the chloroplast ultrastructural damage in the mesophyll cells and thus maintained higher photosynthetic efficiency. Moreover, AM inoculation led to significant enhancements in the enzyme activities and gene expressions of superoxide dismutase, catalase, ascorbate peroxidase, glutathione reductase, and monodehydroascorbate reductase in watermelon leaves upon drought imposition. Consequently, AM plants exhibited lower accumulation of MDA, H2O2 and compared with non-mycorrhizal plants. Under drought stress, the soluble sugar and proline contents were significantly increased, and further enhancements were observed by pre-treating the drought-stressed plants with AM. Taken together, our findings indicate that mycorrhizal colonization enhances watermelon drought tolerance through a stronger root system, greater protection of photosynthetic apparatus, a more efficient antioxidant system and improved osmoregulation. This study contributes to advances in the knowledge of AM-induced drought tolerance.

Alleviative effects from boswellic acid on acetaminophen-induced hepatic injury.

Protective effects of boswellic acid (BA) against acetaminophen (APAP)-induced hepatotoxicity in Balb/ cA mice were examined. BA, at 0.05 or 0.1%, was supplied for 4 weeks. Acute liver injury was induced by APAP treatment. Results showed that BA intake increased hepatic BA bioavailability. APAP treatment decreased glutathione (GSH) level, increased reactive oxygen species (ROS) and oxidized glutathione (GSSG) production; and lowered activity and protein expression of glutathione reductase (GR) and heme oxygenase (HO)-1 in liver. BA intake at both doses alleviated subsequent APAP-induced oxidative stress by retaining GSH content, decreasing ROS and GSSG formations, reserving activity and expression of GR and HO-1 in liver, and lowering hepatic cytochrome P450 2E1 activity and expression. APAP treatment enhanced hepatic levels of interleukin-6, tumor necrosis factor-alpha and monocyte chemoattractant protein-1. BA pre-intake diminished APAP-induced release of those inflammatory cytokines and chemokines. APAP upregulated hepatic protein expression of toll-like receptor (TLR)-3, TLR-4, MyD88, nuclear factor kappa B (NF-κB) p50, NF-κB p65 and JNK. BA pre-intake at both doses suppressed the expression of NF-κB p65 and p-JNK, and only at 0.1% down-regulated hepatic TLR-3, TLR-4 and MyD88 expression. APAP led to obvious foci of inflammatory cell infiltration in liver, determined by H&E stain. BA intake at both doses attenuated hepatic inflammatory infiltration. These findings support that boswellic acid is a potent hepatoprotective agent.

Novel piperazine core compound induces death in human liver cancer cells: possible pharmacological properties.

The current study evaluates the cytotoxic mechanism of a novel piperazine derivate designated as PCC against human liver cancer cells. In this context, human liver cancer cell lines, SNU-475 and 243, human monocyte/macrophage cell line, CRL-9855, and human B lymphocyte cell line, CCL-156, were used to determine the IC50 of PCC using the standard MTT assay. PCC displayed a strong suppressive effect on SNU-475 and SNU-423 cells with an IC50 value of 6.98 ± 0.11 μg/ml and 7.76 ± 0.45 μg/ml respectively, after 24 h of treatment. Significant dipping in the mitochondrial membrane potential and elevation in the released of cytochrome c from the mitochondria indicated the induction of the intrinsic apoptosis pathway by PCC. Activation of this pathway was further evidenced by significant activation of caspase 3/7 and 9. PCC was also shown to activate the extrinsic pathways of apoptosis via activation of caspase-8 which is linked to the suppression of NF-ƙB translocation to the nucleus. Cell cycle arrest in the G1 phase was confirmed by flow cytometry and up-regulation of glutathione reductase expression was quantified by qPCR. This study suggests that PCC is a simultaneous inducer of intrinsic and extrinsic pathways of apoptosis in liver cancer cell lines.

Mechanism of action of novel piperazine containing a toxicant against human liver cancer cells.

The purpose of this study was to assess the cytotoxic potential of a novel piperazine derivative (PCC) against human liver cancer cells. SNU-475 and 423 human liver cancer cell lines were used to determine the IC50 of PCC using the standard MTT assay. PCC displayed a strong suppressive effect on liver cancer cells with an IC50 value of 6.98 ± 0.11 µM and 7.76 ± 0.45 µM against SNU-475 and SNU-423 respectively after 24 h of treatment. Significant dipping in the mitochondrial membrane potential and elevation in the released of cytochrome c from the mitochondria indicated the induction of the intrinsic apoptosis pathway by PCC. Activation of this pathway was further evidenced by significant activation of caspase 3/7 and 9. PCC was also shown to activate the extrinsic pathways of apoptosis via activation of caspase-8 which is linked to the suppression of NF-κB translocation to the nucleus. Cell cycle arrest in the G1 phase was confirmed by flow cytometry and up-regulation of glutathione reductase expression was quantified by qPCR. Results of this study suggest that PCC is a potent anti-cancer agent inducing both intrinsic and extrinsic pathways of apoptosis in liver cancer cell lines.

Role of oxidative stress in the pathophysiology of Toxoplasma gondii infection.

Oxidative stress (OS) plays an essential role in the pathogenesis of common neurodegenerative diseases. We have previously shown that Toxoplasma gondii (T. gondii) induces high nitric oxide (NO) production, glial activation, and apoptosis that altogether cause severe neuropathology in toxoplasma encephalitis (TE). The objective of this study was to investigate the cytotoxic effect of OS and to identify a correlation between the causes of T. gondii induced neuropathology. Expression levels of glutathione reductase (GR), Cu/Zn superoxide dismutase (SOD1), neuron specific enolase (NSE), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were investigated. Results of the study revealed that the levels of GR (P <0.005) and NSE (P <0.001) expression in the brain tissue markedly increased while SOD1 activity decreased (P <0.001) in the infected group compared to the non-infected group. In addition, intense staining for 8-OHdG (P <0.05) was observed both in the nucleus and the cytoplasm of neurons and glial cells that underwent OS. These results were reasonable to suggest that T. gondii-mediated OS might play a pivotal role and a different type of role in the mechanism of neurodegeneration/neuropathology in the process of TE. The results also clearly indicated that increased levels of NO and apoptosis might contribute to OS-related pathogenesis of TE. As a result, OS and expression of NSE might give an idea of the disease progress and may have a critical diagnostic significance for patients with T. gondii infection.

Carbonated soft drinks induce oxidative stress and alter the expression of certain genes in the brains of Wistar rats.

In Saudi Arabia, the consumption of carbonated soft drinks is common and often occurs with each meal. Carbonated soft drink consumption has been shown to exhibit effects on the liver, kidney and bone. However, the effects of these soft drinks on brain activity have not been widely examined, particularly at the gene level. Therefore, the current study was conducted with the aim of evaluating the effects of chronic carbonated soft drink consumption on oxidative stress, brain gene biomarkers associated with aggression and brain histology. In total, 40 male Wistar rats were divided into four groups: Group 1 served as a control and was provided access to food and water ad libitum; and groups 2‑4 were given free access to food and carbonated soft drinks only (Cola for group 2, Pepsi for group 3 and 7‑UP for group 4). Animals were maintained on these diets for 3 consecutive months. Upon completion of the experimental period, animals were sacrificed and serological and histopathological analyses were performed on blood and tissues samples. Reverse transcription‑polymerase chain reaction was used to analyze alterations in gene expression levels. Results revealed that carbonated soft drinks increased the serum levels of malondialdehyde (MDA). Carbonated soft drinks were also observed to downregulate the expression of antioxidants glutathione reductase (GR), catalase and glutathione peroxidase (GPx) in the brain when compared with that in the control rats. Rats administered carbonated soft drinks also exhibited decreased monoamine oxidase A (MAO‑A) and acetylcholine esterase (AChE) serum and mRNA levels in the brain. In addition, soft drink consumption upregulated mRNA expression of dopamine D2 receptor (DD2R), while 5-hydroxytryptamine transporter (5‑HTT) expression was decreased. However, following histological examination, all rats had a normal brain structure. The results of this study demonstrated that that carbonated soft drinks induced oxidative stress and altered the expression of certain genes that are associated with the brain activity and thus should be consumed with caution.

Resveratrol Protects against Titanium Particle-Induced Aseptic Loosening Through Reduction of Oxidative Stress and Inactivation of NF-κB.

Aseptic implant loosening is closely associated with chronic inflammation induced by implant wear debris, and reactive oxygen species (ROS) play an important role in this process. Resveratrol, a plant compound, has been reported to act as an antioxidant in many inflammatory conditions; however, its protective effect and mechanism against wear particle-induced oxidative stress remain unknown. In this study, we evaluated resveratrol's protective effects against wear particle-induced oxidative stress in RAW 264.7 macrophages. At non-toxic concentrations, resveratrol showed dose-dependent inhibition of nitric oxide (NO) production, ROS generation, and lipid peroxidation. It also downregulated the gene expression of oxidative enzymes, including inducible nitric oxide synthase (iNOS) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX)-1 and NOX-2, and promoted the gene expression and activities of antioxidant enzymes, including catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GR), and glutathione peroxidase (GPx). This protective effect against wear particle-induced oxidative stress was accompanied by a reduction of gene expression and release of tumor necrosis factor-α (TNF-α), and decreased gene expression and phosphorylation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). These findings demonstrate that resveratrol can inhibit wear particle-induced oxidative stress in macrophages, and may exert its antioxidant effect and protect against aseptic implant loosening.

Effects of selenium supplementation on the oxidative state of acute heat stress-exposed quails.

This study aimed to evaluate the effect of heat stress (HS) and selenium supplementation on markers of stress, meat quality and gene expression. For this, meat quails of 42days of age were fed a diet that either met [0.33mg/kg, nutritional demand for selenium (SS)] or did not meet [0.11mg/kg, selenium deficient (SD)] the nutritional demands for selenium during the 7days of evaluation. In addition, the animals were kept at either a thermal comfort temperature (25°C) or exposed to HS (38°C for 24h). Glutathione synthetase (GSS), glutathione reductase (GSR) and uncoupling protein (UCP) gene expression were influenced by the interaction between temperature and diet. Animals subjected to HS and fed the SS diet exhibited the highest GSS and GSR gene expression. In terms of UCP gene expression, the lowest values were observed in HS animals on the SD diet. Glutathione peroxidase 7 (GPX7) gene expression, body temperature (BT) and creatine kinase (CK) activity were influenced by both selenium supplementation and HS. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) activity and creatinine content all were influenced by the diet/environment interaction. The highest AST activity, ALT activity and creatinine levels were observed in animals that were both on the SD diet and exposed to HS. HS animals also exhibited an increased heterophil/lymphocyte ratio and lower triiodothyronine (T3) hormone levels than birds that remained at the comfortable temperature. Animals subjected to HS and fed with selenium supplemented diet showed better results regarding gene expression and, thus, better results for the activities of enzymes used as stress markers, which could be due to the higher antioxidant capacity provided by the action of the studied genes.

Mechanism of Action of the Novel Nickel(II) Complex in Simultaneous Reactivation of the Apoptotic Signaling Networks Against Human Colon Cancer Cells.

The aim of this study was to evaluate the cytotoxic potential of a novel nickel(II) complex (NTC) against WiDr and HT-29 human colon cancer cells by determining the IC50 using the standard MTT assay. The NTC displayed a strong suppressive effect on colon cancer cells with an IC50 value of 6.07 ± 0.22 μM and 6.26 ± 0.13 μM against WiDr and HT-29 respectively, after 24 h of treatment. Substantial reduction in the mitochondrial membrane potential and increase in the release of cytochrome c from the mitochondria directed the induction of the intrinsic apoptosis pathway by the NTC. Activation of this pathway was further evidenced by significant activation of caspase 3/7 and 9. The NTC was also shown to activate the extrinsic pathway of apoptosis via activation of caspase-8 which is linked to the suppression of NF-κB translocation to the nucleus. Cell cycle arrest in the G1 phase was confirmed by flow cytometry and up-regulation of glutathione reductase expression was quantified by qPCR. Results of the current work indicates that NTC possess a potent cancer cell abolishing activity by simultaneous induction of intrinsic and extrinsic pathways of apoptosis in colon cancer cell lines.

Modulation of Brain Glutathione Reductase and Peroxiredoxin 2 by α-Tocopheryl Phosphate.

α-Tocopheryl phosphate (αTP) is a phosphorylated form of α-tocopherol. Since it is phosphorylated in the hydroxyl group that is essential for the antioxidant property of α-tocopherol, we hypothesized that αTP would modulate the antioxidant system, rather than being an antioxidant agent per se. α-TP demonstrated antioxidant activity in vitro against iron-induced oxidative stress in a mitochondria-enriched fraction preparation treated with 30 or 100µM α-TP. However, this effect was not observed ex vivo with mitochondrial-enriched fraction from mice treated with an intracerebroventricular injection of 0.1 or 1nmol/site of αTP. Two days after treatment (1nmol/site αTP), peroxiredoxin 2 (Prx2) and glutathione reductase (GR) expression and GR activity were decreased in cerebral cortex and hippocampus. Glutathione content, glutathione peroxidase, and thioredoxin reductase activities were not affected by αTP. In conclusion, the persistent decrease in GR and Prx2 protein content is the first report of an in vivo effect of αTP on protein expression in the mouse brain, potentially associated to a novel and biologically relevant function of this naturally occurring compound.