Expression Of Glutathione Reductase Research Articles

Episomal expression of human glutathione reductase (HuGR) in Leishmania sheds light on evolutionary pressure for unique redox metabolism pathway: Impaired stress tolerance ability of Leishmania donovani

Trypanothione based redox metabolism is unique to the Trypanosomatida family. Despite extensive studies on redox metabolism of Leishmania parasites, a prominent question of why Leishmania adopt this unique redox pathway remains elusive. We have episomally expressed human glutathione reductase (HuGR) in Leishmania donovani (LdGR+) and investigated its effect. LdGR+ strain has slower growth compared to the wild type (Ld) indicating decreased survival ability of the strain. Further, LdGR+ strain showed enhanced accumulation of intracellular reactive oxygen species (ROS) and more sensitivity to the anti-leishmanial drug, Miltefosine, inferring increased stress level. In contrast, the expression analyses of genes specific to redox metabolism were increased significantly in LdGR+ strain compared to wild type. Lower infectivity index of the LdGR+ strain substantiated the above findings and indicated that the expression of HuGR reduces the stress tolerance ability of the parasite. From molecular docking studies with HuGR, it was observed that oxidized trypanothione (TS2) binds much better than oxidized glutathione (GS2). These results also give us hints that the parasite is losing infectivity potential due to an overall increase in intracellular stress caused with the expression of HuGR, showcasing a possible role of evolutionary pressure on the Leishmania parasites posed by HuGR.

Conotoxin MVIIA improves cell viability and antioxidant system after spinal cord injury in rats.

This study evaluates whether intrathecal MVIIA injection after spinal cord injury (SCI) elicits neuroprotective effects. The test rats were randomly distributed into six groups— sham, placebo, MVIIA 2.5 μM, MVIIA 5 μM, MVIIA 10 μM, and MVIIA 20 μM—and were administered the treatment four hours after SCI. After the optimal MVIIA dose (MVIIA 10 μM) was defined, the best time for application, one or four hours, was analyzed. Locomotor hind limb function and side effects were assessed. Forty-eight hours after the injury and immediately after euthanasia, spinal cord segments were removed from the test rats. Cell viability, reactive oxygen species, lipid peroxidation, and glutamate release were investigated. To examine the MVIIA mechanism of action, the gene expressions of pro-apoptotic (Bax, nNOS, and caspase-3, -8, -9, -12) and anti-apoptotic (Bcl-xl) factors in the spinal cord tissue samples were determined by real-time PCR, and the activities of antioxidant enzymes were also investigated. Application of intrathecal MVIIA 10 μM four hours after SCI prompted a neuroprotective effect: neuronal death decreased (22.46%), oxidative stress diminished, pro-apoptotic factors (Bax, nNOS, and caspase-3, -8) were expressed to a lesser extent, and mitochondrial viability as well as anti-apoptotic factor (Bcl-xl) expression increased. These results suggested that MVIIA provided neuroprotection through antioxidant effects. Indeed, superoxide dismutase (188.41%), and glutathione peroxidase (199.96%), reductase (193.86%), and transferase (175.93%) expressions increased. Therefore, intrathecal MVIIA (MVIIA 10 μM, 4 h) application has neuroprotective potential, and the possible mechanisms are related to antioxidant agent modulation and to intrinsic and extrinsic apoptotic pathways.

Spermidine application alleviates salinity damage to antioxidant enzyme activity and gene expression in alfalfa.

We investigated whether spermidine (Spd) application alleviates salinity-induced damage in alfalfa (Medicago sativa L), and explored defence mechanisms associated with stress-related ion balance, antioxidant metabolism, and gene expression. We examined the response of 30-day-old alfalfa maintained in hydroponic culture tests for 7 days and subjected to one of six treatments: half-strength Hoagland solution (control); 1% NaCl; 10 μM Spd + 1% NaCl; 20 μM Spd + 1% NaCl; 40 μM Spd + 1% NaCl; and 60 μM Spd + 1% NaCl. In salinity-stressed plants, chlorophyll b, chlorophyll a + b, and total protein showed significant decreases, while marked increases were detected in relative electrolyte leakage, H2O2 content, glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), glutathione reductase (GR) activity, the Na+/K+ ratio, and APX1, APX2, GR, and SOD gene expression levels. Chlorophyll a and total protein content markedly increased under exogenous application of 20 μM Spd, while H2O2 content, GSH, SOD, CAT, POD, GR activity, the Na+/K+ ratio, and APX2, GR, and SOD expression levels all decreased. These results indicated that exogenous application of 20 μM spermidine effectively alleviates salinity-induced damage in alfalfa. These findings could benefit alfalfa cultivation and promote the development and utilization of saline-alkali soil.

Dietary supplementation with taurine improves ability to resist ammonia stress in hybrid snakehead (Channa maculatus♀ × Channa argus♂)

This study determined the effect of dietary supplementation with taurine on plasma biochemical indices, blood cell apoptosis rate, survival rate and expression of catalase (CAT), glutathione reductase (GR) and heat-shock protein 70 (HSP70) gene in juvenile hybrid snakehead under ammonia stress. Six diets were formulated to contain 0, 3.0, 6.0, 9.0, 12.0 and 15.0 g/kg taurine. Each diet was fed to triplicate groups of fish in cylindrical tanks. After 8 weeks of feeding, 20 fish per tank were exposed to ammonia stress (total ammonia nitrogen = 200 mg/L) for 48 hr. The results showed that, after ammonia stress, plasma alkaline phosphatase (ALP), triacylglycerol (TG) levels and survival rate significantly decreased (p < 0.05) while plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea nitrogen (BUN), respiratory burst, blood cell apoptosis rate, hepatic CAT, GR and HSP70 mRNA expression levels significantly increased (p < 0.05). On the other hand, dietary supplementation with taurine significantly reduced levels of BUN, respiratory burst and blood cell apoptosis rate. Supplemented groups significantly increased relative mRNA expression of hepatic CAT, GR and HSP70 as well as increased survival rate (p < 0.05). These results indicated that dietary supplementation with taurine improved ability to resist ammonia stress in hybrid snakehead.

Correction to: Comparative Analysis of the Expression of Glutathione Peroxidase and Glutathione Reductase Genes in Human Sperm after Cryopreservation.

The second author's name should read A. Yu. Romanov.

Using A “Superrooting”Cultivar of Taxus Chinensis Var. Mairei to Unravel Antioxidative Enzymes’ and Micrornas’ Role on Adventitious Rooting

Rooting of cuttings is very important for production of economically important plants. We produced thousands of plantlets in Taxus chinensisvar. mairei using the technology of rooting of cuttings and identified two types of rooted cuttings, one with low rate of root formation and another with high rate of root formation. To determine the physiological role of antioxidative enzymes and microRNAs during the process of rooting, we measured the levels of these antioxidative enzymes and microRNAs in the stem portion, needles, roots, and basal portion of cuttings. Compared to the cuttings with low rate of root formation, cuttings with high rate of root formation had higher expression of polyphenoloxidase (PPO), catalase (CAT), peroxidase (POD), ascorbate peroxidase (APOX), glutathione reductase (GR), and superoxide dismutase (SOD) in the adventitious roots and basal portion of the rooted cuttings 77 days after planting. In the basal portion of cuttings, the content of thiobarbituric acid reactive substances (TBARS) and total phenols were decreased and the content of antioxidants was increased, but they did not changed in the needles of cuttings during planting. Analysis of microRNAs by quantitative realtime PCR demonstrated that expression of miR162, miR408, and miR857 increases in the basal portion of cuttings, but not in the stem portion of cuttings, 77 days after planting. Expression of miR408 and miR857 were also increased in the needles of cuttings 77 days after planting. Changes of these antioxidative enzymes and microRNAs associated with the rooting features of T. chinensisvar. maireicuttings and their functions have been discussed.

Comparative Analysis of the Expression of Glutathione Peroxidase and Glutathione Reductase Genes in Human Sperm after Cryopreservation.

We analyzed the effect of cryopreservation on the expression of glutathione peroxidase (GPX1) and glutathione reductase (GSR) genes in human sperm cells (15 sperm samples from fertile donors and 10 samples from infertile patients). The relative expression of GPX1 and GSR genes was determined by real-time PCR. The rate of post-thaw recovery was 2.1 times higher in the group of fertile donors. A significant increase in the expression of GPX1, but not GSR, was observed in sperm samples from infertile patients, while in patients with infertility, GPX1 expression significantly decreased after cryopreservation/thawing, in samples from fertile donors after the same procedure it increased to the level observed in the sperm samples from infertile patients. A positive correlation was revealed between GPX1 expression and sperm cryotolerance.

P-148 - Early reductive stress followed by a late onset oxidative stress in acute myocardial infarction

Introduction The idea that the cells might suffer from reductive rather than oxidative stress and that such stress may be relevant in pathophysiology has gained momentum. Aim We aimed at studying markers of oxidative stress and damage as well as the expression of antioxidant enzymes in a swine model of acute myocardial infarction (AMI) followed by reperfusion. Results and Discussion We found an increase in the GSH to GSSG ratio, a decrease in protein glutathionylation and a decrease in p38 MAPK phosphorylation after 90 minutes of ischaemia in heart samples. It was accompanied by an increase in the expression of Thioredoxin (TrX) and Peroxiredoxin (PrX) and a decrease in the expression of Glutathione Peroxidase (Gpx). One week after reperfusion an increase in lipid peroxidation, protein glutathionylation and protein carbonylation was accompanied by a massive increase in the expression of TrX, PrX, GPx, Glutathione Reductase (GR) and Glucose 6 Phosphate Dehydrogenase (G6PD). These increments seemed to be Nrf-2 independent and most of them were maintained in the heart samples one month after reperfusion. Conclusion We have found an early reductive stress followed by a late onset oxidative stress in AMI followed by reperfusion.

Increased Glutathione Reductase Expression and Activity in Colorectal Cancer Tissue Samples: An Investigational Study in Mashhad, Iran

Background: Glutathione reductase is an important enzyme in oxidative metabolism that provides reduced glutathione from its oxidized form in the cells. The role of oxidative stress in tumor tissues has led us to investigate the gene expression and activity of this enzyme in tumor and adjacent resected margins of colorectal cancer tissues, one of the most common malignancies in humans. Methods: We conducted this study on 15 Iranian colorectal cancer patients. RNA was extracted from fresh colon tissues that included tumor and anatomically normal margin tissue. Expression of the glutathione reductase gene was determined using realtime PCR by the ΔΔCt relative quantification method. The gene expression results were standardized with glyceraldehyde 3-phosphate dehydrogenase as the endogenous reference gene. In addition, we measured enzyme activity of glutathione reductase with a commercial kit based on a colorimetric assay. Results: The tumor tissue had higher expression of glutathione reductase compared to the margin tissue (P=0.005). There was significantly greater glutathione reductase enzyme activity in the tumor tissue (116.9±34.31 nmol/min/ml) compared to the noncancerous adjacent tissues (76.7±36.85 nmol/min/ml; P=0.003). Conclusion: These data showed increased glutathione reductase expression and enzyme activity in colorectal tumor tissue. Given the key role of glutathione in synthesis of dNTPs for DNA repair with the glutaredoxin system, the increased glutathione reductase expression and activity might be a reflection of hyperactivity of this enzyme in DNA synthesis and the repair process in colorectal cancer cells.

Differential response of antioxidant defense in HepG2 cells on exposure of Livotrit®, in a concentration dependent manner

Livotrit®, a polyherbal formulation (Zandu, India) is commonly prescribed for liver health. The present study was undertaken to elucidate possible mechanism of antioxidant potential of Livotrit®. Livotrit® exhibited concentration dependent radical scavenging activity, inhibition of lipid peroxidation as well as activation and gene expression of antioxidant enzymes. Interestingly, lower concentration of Livotrit® (0.05%) significantly increased activities and gene expression of catalase, Glutathione reductase (GR) and Gluthathione peroxidase (GPx), while higher concentration of Livotrit® (0.5%) significantly increased antioxidant enzyme Heme-oxygenase 1(HO-1) and not catalase (CAT), GR and GPx. Transcription factor, Nuclear factor erythroid 2-related factor 2 (Nrf2) required for expression of catalase, GR, GPx and HO-1 was efficiently translocated into the nucleus at both concentrations. Inspite of this, concentration dependent activation of these enzymes was found to be mediated through miRNAs involved in regulation of their gene expression.

Changes of lipid peroxidation and glutathione redox system, and expression of glutathione peroxidase regulatory genes as effect of short-term aflatoxin B1 exposure in common carp

Lipid peroxidation, glutathione content, glutathione peroxidase activity and gene expression of transcription factors, glutathione peroxidase, glutathione synthetase and glutathione reductase was investigated in common carp liver. Short term (24 h) exposure of aflatoxin B1 at different doses (100, 200 and 400 μg AFB1 kg−1 feed) was used. It was found that conjugated dienes and trienes elevated after 16 h, while thiobarbituric acid reactive substances content increased only at the lowest dose after 16 and 24 h of exposure. Glutathione content showed higher levels than control after 16 h of exposure and glutathione peroxidase (GPx4) activity was higher in all of the AFB1 treated than the control group after 8 h of exposure. Gene expression of transcription factors showed dual response. Expression of keap1 gene down-regulated after 8 h and 16 h and nrf2 gene after16 h, but up-regulated after 24 h of exposure in the lowest, and highest dose groups. Expression of gpx4a and gpx4b genes down-regulated after 8 h and induction was found after 16 and 24 h of exposure, irrespective of the dose. The results indicated that low dose of AFB1 provokes oxidative stress earlier than higher doses, which activated the Keap1-Nrf2 pathway. At higher doses this pathway activated later, but preformed GPx4 effectively prevented lipid peroxidation.

Effects of diverse stresses on gene expression and enzyme activity of glutathione reductase in Brassica campestris.

A novel glutathione reductase gene (GR2) was isolated from Brassica campestris Longyou 6 by rapid isolation of cDNA ends (RACE). The full-length of cDNA of GR2 was 2073 bp, with an open reading frame (ORF) of 1692 bp. GR2 encoded a protein of 563 amino acids with a deduced molecular mass of about 60.7 kDa and an isoelectric point of 7.9. The real-time quantitative PCR results showed that GR2 was expressed in the roots, stems and leaves in B. campestris, among which the expression of GR2 in leaves was the highest. The transcript levels of GR1 and GR2, and the enzyme activity of glutathione reductase (GR) increased in response to cold temperature, high temperature, drought stress, and salt stress. The results suggested that GR played an important role in coping with diverse stresses in B. campestris. When abscisic acid (ABA) pretreatment was applied before cold temperature, high temperature, drought stress, salt stress, the expression levels of GR1and GR2, and the activity level of GR all significantly increased compared with the single stress, which indicated that ABA could induce GR1 and GR2 gene transcription and GR activity. However, when MAPKK inhibitor (U0126) pretreatment was applied before the above stresses, the expression levels of GR1and GR2 and the activity level of GR significantly decreased compared with the single stress suggesting that U0126 inhibited GR1 and GR2 gene transcription and GR activity.

Glutathione reductase mediates drug resistance in glioblastoma cells by regulating redox homeostasis

Glutathione (GSH) and GSH-related enzymes constitute the most important defense system that protects cells from free radical, radiotherapy, and chemotherapy attacks. In this study, we aim to explore the potential role and regulatory mechanism of the GSH redox cycle in drug resistance in glioblastoma multiforme (GBM) cells. We found that temozolomide (TMZ)-resistant glioma cells displayed lower levels of endogenous reactive oxygen species and higher levels of total antioxidant capacity and GSH than sensitive cells. Moreover, the expression of glutathione reductase (GSR), the key enzyme of the GSH redox cycle, was higher in TMZ-resistant cells than in sensitive cells. Furthermore, silencing GSR in drug-resistant cells improved the sensitivity of cells to TMZ or cisplatin. Conversely, the over-expression of GSR in sensitive cells resulted in resistance to chemotherapy. In addition, the GSR enzyme partially prevented the oxidative stress caused by pro-oxidant L-buthionine -sulfoximine. The modulation of redox state by GSH or L-buthionine -sulfoximine regulated GSR-mediated drug resistance, suggesting that the action of GSR in drug resistance is associated with the modulation of redox homeostasis. Intriguingly, a trend toward shorter progress-free survival was observed among GBM patients with high GSR expression. These results indicated that GSR is involved in mediating drug resistance and is a potential target for improving GBM treatment.

Castasterone confers copper stress tolerance by regulating antioxidant enzyme responses, antioxidants, and amino acid balance in B. juncea seedlings

The aim of the present study was to explore the effect of exogenous application of castasterone (CS) on physiologic and biochemical responses in Brassica juncea seedlings under copper (Cu) stress. Seeds were pre-soaked in different concentrations of CS and grown for 7 days under various levels of Cu. The exposure of B. juncea to higher levels of Cu led to decrease of morphologic parameters, with partial recovery of length and fresh weight in the CS pre-treated seedlings. Metal content was high in both roots and shoots under Cu exposure while the CS pre-treatment reduced the metal uptake. Accumulation of hydrogen peroxide (H2O2) and superoxide anion radical (O2-) were chosen as stress biomarker and higher levels of H2O2 (88.89%) and O2- (62.11%) showed the oxidative stress in metal treated B. juncea seedlings, however, CS pre-treatment reduced ROS accumulation in Cu-exposed seedlings. The Cu exposures lead to enhance the plant's enzymatic and non-enzymatic antioxidant system. It was observed that enzymatic activities of ascorbate peroxidase (APOX), dehydroascorbate reductase (DHAR), and glutathione reductase (GR), glutathione perxoidase (GPOX) and gultrathione-s-transferase increased while activity of monodehydroascorbate reductase (MDHAR) decreased under Cu stress. The pre-treatment with CS positively affected the activities of enzymes. RT-PCR analysis showed that mRNA transcript levels were correlated with total enzymatic activity of DHAR, GR, GST and GSH. Increase in the gene expression of DHAR (1.85 folds), GR (3.24 folds), GST-1 (2.00 folds) and GSH-S (3.18 folds) was noticed with CS pre-treatment. Overall, the present study shows that Cu exposure induced severe oxidative stress in B. juncea plants and exogenous application of CS improved antioxidative defense system by modulating the ascorbate-glutathione cycle and amino acid metabolism.

Early response of glutathione- and thioredoxin-dependent antioxidant defense systems to Tl(I)- and Tl(III)-mediated oxidative stress in adherent pheochromocytoma (PC12adh) cells.

Thallium (Tl) is a toxic heavy metal that causes oxidative stress both in vitro and in vivo. In this work, we evaluated the production of oxygen (ROS)- and nitrogen (RNS)-reactive species in adherent PC12 (PC12adh) cells exposed for 0.5-6h to Tl(I) or Tl(III) (10-100µM). In this system, Tl(I) induced mostly H2O2 generation while Tl(III) induced H2O2 and ONOO·- generation. Both cations enhanced iNOS expression and activity, and decreased CuZnSOD expression but without affecting its activity. Tl(I) increased MnSOD expression and activity but Tl(III) decreased them. NADPH oxidase (NOX) activity remained unaffected throughout the period assessed. Oxidant levels returned to baseline values after 6h of incubation, suggesting a response of the antioxidant defense system to the oxidative insult imposed by the cations. Tl also affected the glutathione-dependent system: while Tl(III) increased glutathione peroxidase (GPx) expression and activity, Tl(I) and Tl(III) decreased glutathione reductase (GR) expression. However, GR activity was mildly enhanced by Tl(III). Finally, thioredoxin-dependent system was evaluated. Only Tl(I) increased 2-Cys peroxiredoxins (2-Cys Prx) expression, although both cations increased their activity. Tl(I) increased cytosolic thioredoxin reductase (TrxR1) and decreased mitochondrial (TrxR2) expression. Tl(III) had a biphasic effect on TrxR1 expression and slightly increased TrxR2 expression. Despite of this, both cations increased total TrxR activity. Obtained results suggest that in Tl(I)-exposed PC12adh cells, there is an early response to oxidative stress mainly by GSH-dependent system while in Tl(III)-treated cells both GSH- and Trx-dependent systems are involved.

Glutathione oxidation in response to intracellular H2O2: Key but overlapping roles for dehydroascorbate reductases

ABSTRACTGlutathione is a pivotal molecule in oxidative stress, during which it is potentially oxidized by several pathways linked to H2O2 detoxification. We have investigated the response and functional importance of 3 potential routes for glutathione oxidation pathways mediated by glutathione S-transferases (GST), glutaredoxin-dependent peroxiredoxins (PRXII), and dehydroascorbate reductases (DHAR) in Arabidopsis during oxidative stress. Loss-of-function gstU8, gstU24, gstF8, prxIIE and prxIIF mutants as well as double gstU8 gstU24, gstU8 gstF8, gstU24 gstF8, prxIIE prxIIF mutants were obtained. No mutant lines showed marked changes in their phenotype and glutathione profiles in comparison to the wild-type plants in either optimal conditions or oxidative stress triggered by catalase inhibition. By contrast, multiple loss of DHAR functions markedly decreased glutathione oxidation triggered by catalase deficiency. To assess whether this effect was mediated directly by loss of DHAR enzyme activity, or more indirectly by upregulation of other enzymes involved in glutathione and ascorbate recycling, we measured expression of glutathione reductase (GR) and expression and activity of monodehydroascorbate reductases (MDHAR). No evidence was obtained that either GRs or MDHARs were upregulated in plants lacking DHAR function. Hence, interplay between different DHARs appears to be necessary to couple ascorbate and glutathione pools and to allow glutathione-related signaling during enhanced H2O2 metabolism.

The Expression and Enzyme Activity of the Cytosolic Glutathione Reductase was Upregulated by Nitrogen-Deficiency in Wheat (Triticum aestivum L.) Grain

The Expression and Enzyme Activity of the Cytosolic Glutathione Reductase was Upregulated by Nitrogen-Deficiency in Wheat (<i>Triticum aestivum</i> L.) Grain

Abstract 40: Investigation into Heart Aging

Background: Aging is a well-known contributing factor for heart failure, which is the leading cause of death world-wide. However, the underlying mechanisms of heart aging are less clear. Methods and Results: We found that the overall heart size, heart weight, and cardiomyocyte size were increased in aged mice (24 months). Cardiac fibrosis was also found in old mice. Therefore, aging induced cardiac hypertrophy and remodeling. Concomitantly, heart function declined significantly in aged mice, as evidenced by decreases in fraction shorting, ejection fraction, left ventricular stroke volume, and cardiac output. Renal and circulating Klotho levels were dramatically decreased, suggesting that there may be association between a decrease in Klotho and heart failure in aged mice. Using Klotho mutant homozygous (KL-/-) mice, we found that Klotho deficiency caused cardiac hypertrophy and heart failure. Interestingly, treatment with secreted Klotho prevented cardiac hypertrophy, remodeling and heart failure in aged mice and KL (-/-) mice. Secreted Klotho treatment attenuated excessive cardiac oxidative stress and apoptosis in old mice and KL (-/-) mice. In this study, all KL (-/-) mice were fed with low-phosphate diet which maintained serum phosphate at the normal level, suggesting that the cardioprotective effects of secreted Klotho were independent of phosphate metabolism. Mechanistically, Klotho deficiency suppressed glutathione reductase (GR) expression and activity in the heart through downregulation of a transcription factor Nrf2. Furthermore, heart-specific overexpression of GR prevented aging- and Klotho deficiency-induced heart failure, excessive cardiac oxidative stress and apoptosis in old mice and KL (-/-) mice. Conclusions: Klotho deficiency plays an important role in aging-related heart failure. Secreted Klotho protects against heart aging via activation of glutathione reductase which attenuates cardiac oxidative stress, apoptosis and fibrosis.

Inhibition of Oxidative Stress through the Induction of Antioxidant Enzymes of Pigmented Rice Bran in HEK-293 Cells

The cellular antioxidant enzymes play an essential role on the protection of oxidative stress. Pigmented rice bran is the major sources of phytochemicals and elicits antioxidant property. However, the effects of pigmented rice bran on the upregulation of cellular antioxidant enzymes are incompletely understood. In this study, we demonstrated that treatment of HEK-293 cells with pigmented rice bran extracts (200 μg/mL) from Red Hawm, Red Rose, Black Sukhothai-II, and Kum Doisaket strains significantly inhibited H2O2-induced intracellular ROS production. These pigmented rice bran extracts induced mRNA expression of glutathione peroxidase-1 (GPx-1), glutathione reductase and catalase. Additionally, treatment with these rice bran extract also increased protein expression of GPx-1 and catalase. Thus, these pigmented rice bran extracts exert the cellular antioxidant effects by decreasing ROS generation as well as increasing the production of antioxidant enzymes.

P 36 Association of placental oxidative stress and pregnancy outcome in patients with hypertensive disorders of pregnancy – A pilot study in an Indian population

Objectives To assess the placental oxidative stress factors in various types of hypertensive disorders of pregnancy and to correlate with the pregnancy outcome. Methods Placental samples from Hypertensive disorders of pregnancy (HDP) patients and the control pregnant women (CPW) were collected. The levels of oxidative stress parameters MDA, Total antioxidant status (TAS) and protein carbonylation (PCO) were assessed in the placental lysates. Also the placental expression of antioxidant enzymes superoxide dismutase (SOD), Glutathione peroxidase (GPX1), Glutathione Reductase (GSH), catalase and stress sensitive serine kinase proteins ERK, p38-MAPK, JNK, IKBα and NOX-4 were found out by western blotting in HDP (gestational hypertension, Preeclampsia- eclampsia) and CPW. The Pregnancy outcomes like the gestational age at the time of delivery (GA) and birthweight (BW) and APGAR score of the baby also were measured. Results The GA, BW and APGAR score of the baby were found to be significantly lower in Preeclampsia and Eclampsia compared to CPW. The levels oxidative stress parameters MDA and PCO were elevated and the TAS were decreased in HDP compared to CPW. The placental expression of pERK, pNrf-2/Nrf-2, NOX-4 and IkBα were found to be elevated whereas the expression of CAT, JNK, pP38MAPK were found to be decreased in HDP when compared to CPW. Also a negative correlation was observed between the o0xidative stress markers and the pregnancy outcome in HDP. Conclusions An increased placental oxidative stress and a poor birth outcome were observed in hypertensive disorders of pregnancy. Download : Download high-res image (419KB) Download : Download full-size image Download : Download high-res image (231KB) Download : Download full-size image Download : Download high-res image (723KB) Download : Download full-size image