Glutathione Peroxidase 3 Levels Research Articles

Evaluation of Some Immunological and DNA Damage Parameters among Patients with Rheumatoid Arthritis

Rheumatoid arthritis (RA) can cause permanent joint damage and disability through inflammation in the joints. Other organs, such as blood vessels, lungs, heart, eyes and skin may also get affected. This study aimed to evaluate the changes of some oxidative stress markers including oxidative DNA damage and the clinical outcomes that are associated with Iraqi rheumatoid arthritis patients. Commercial enzyme linked immunosorbent assay (ELISA) kits were applied to evaluate malondialdehyde (MDA), DNA damage marker 8-hydroxy-2-deoxyguanosine (8-OHDG), and glutathione peroxidase 3 (GPX3) levels in serum of 60 patients having RA with ages ranging between 20-70 years and 30 age-matched healthy controls. The results showed a significant increase in MDA levels in RA patients compared with the control group. Also, the levels of GPX3 decreased in RA patients with highly significant differences as compared with healthy control. Highly significant serum levels of oxidative DNA damage in RA patients were observed compared to the control group. Body Mass Index (BMI) results indicted significant differences between RA patients and healthy control. It can, therefore, be concluded that there is a potential role if malondialdehyde, oxidative DNA damage and GPX3 are used as biomarkers for progression of in patients with RA.

Deciphering the associations of selenium distribution in serum GPx-3 and selenoprotein P with cardiovascular risk factors in a healthy population with moderate levels of selenium: The ATTICA study

BackgroundSelenium (Se) is an essential micronutrient, important for human health. The relationship of Se with cardiovascular risk factors is still inconclusive, especially regarding the role of different selenoproteins. The present study evaluated the relation of total serum Se as well as its distribution in plasma selenoproteins, namely glutathione peroxidase 3 (GPx3) and selenoprotein P (SelP) with cardiovascular risk factors in a sex-specific manner, in a healthy population with moderate levels of Se. Methods: A sub-sample from the ATTICA Study’s database, consisting of 398 participants (160 females and 238 males) with data on Se and selenoproteins levels, was considered. GPx3, SelP and the main non-specific serum selenium containing protein, selenoalbumin (SeAlb) were simultaneously determined in human plasma by high-performance liquid chromatography (HPLC) coupled with inductively coupled plasma mass spectrometry (ICP-MS) at baseline. Results: Participants that belong to the highest tertiles of GPx3 and SelP presented the lowest blood pressure. Homocysteine was inversely associated with SelP and its ratio SelP/TSe in both sexes. In males, the lowest tertile of GPx3 showed lower adiponectin levels (0.66 ± 0.21 μg/mL) in comparison to the 2nd tertile of GPx3 (p=0.002), SelP was inversely associated with visceral adipose index (VAI) (-2.29 ± 0.81, p=0.005). Particularly, in males, the middle tertile of SelP had the lowest VAI values. Regarding females, lower Lp(a) concentration by 11.96 ± 5.84 mg/dL was observed in low SelP levels while higher leptin concentration by 2.30 ± 0.73 μg/L and lower fibrinogen concentration by 27.32 ± 13.30 mg/dL was detected in low GPx3 levels. Conclusion: Circulating selenoproteins exert differentiated effects on cardiovascular risk factors, some of them in a sex-specific manner.

Post-GWAS multiomic functional investigation of the TNIP1 locus in Alzheimer's disease highlights a potential role for GPX3.

Recent genome-wide association studies (GWAS) have reported a genetic association with Alzheimer's disease (AD) at the TNIP1/GPX3 locus, but the mechanism is unclear. We used cerebrospinal fluid (CSF) proteomics data to test (n=137) and replicate (n=446) the association of glutathione peroxidase 3 (GPX3) with CSF biomarkers (including amyloid and tau) and the GWAS-implicated variants (rs34294852 and rs871269). CSF GPX3 levels decreased with amyloid and tau positivity (analysis of variance P=1.5×10-5) and higher CSF phosphorylated tau (p-tau) levels (P=9.28×10-7). The rs34294852 minor allele was associated with decreased GPX3 (P=0.041). The replication cohort found associations of GPX3 with amyloid and tau positivity (P=2.56×10-6) and CSF p-tau levels (P=4.38×10-9). These results suggest variants in the TNIP1 locus may affect the oxidative stress response in AD via altered GPX3 levels. Cerebrospinal fluid (CSF) glutathione peroxidase 3 (GPX3) levels decreased with amyloid and tau positivity and higher CSF phosphorylated tau. The minor allele of rs34294852 was associated with lower CSF GPX3. levels when also controlling for amyloid and tau category. GPX3 transcript levels in the prefrontal cortex were lower in Alzheimer's disease than controls. rs34294852 is an expression quantitative trait locus for GPX3 in blood, neutrophils, and microglia.

Association of Glutathione Peroxidase 3 (GPx3) and miR-196a with Carbohydrate Metabolism Disorders in the Elderly.

The escalating prevalence of carbohydrate metabolism disorders (CMDs) prompts the need for early diagnosis and effective markers for their prediction. Hyperglycemia, the primary indicator of CMDs including prediabetes and type 2 diabetes mellitus (T2DM), leads to overproduction of reactive oxygen species (ROS) and oxidative stress (OxS). This condition, resulting from chronic hyperglycemia and insufficient antioxidant defense, causes damage to biomolecules, triggering diabetes complications. Additionally, aging itself can serve as a source of OxS due to the weakening of antioxidant defense mechanisms. Notably, previous research indicates that miR-196a, by downregulating glutathione peroxidase 3 (GPx3), contributes to insulin resistance (IR). Additionally, a GPx3 decrease is observed in overweight/obese and insulin-resistant individuals and in the elderly population. This study investigates plasma GPx3 levels and miR-196a expression as potential CMD risk indicators. We used ELISA to measure GPx3 and qRT-PCR for miR-196a expression, supplemented by multivariate linear regression and receiver operating characteristic (ROC) analysis. Our findings included a significant GPx3 reduction in the CMD patients (n = 126), especially in the T2DM patients (n = 51), and a decreasing trend in the prediabetes group (n = 37). miR-196a expression, although higher in the CMD and T2DM groups than in the controls, was not statistically significant, potentially due to the small sample size. In the individuals with CMD, GPx3 levels exhibited a negative correlation with the mass of adipose tissue, muscle, and total body water, while miR-196a positively correlated with fat mass. In the CMD group, the analysis revealed a weak negative correlation between glucose and GPx3 levels. ROC analysis indicated a 5.2-fold increased CMD risk with GPx3 below 419.501 ng/mL. Logistic regression suggested that each 100 ng/mL GPx3 increase corresponded to a roughly 20% lower CMD risk (OR = 0.998; 95% CI: 0.996-0.999; p = 0.031). These results support the potential of GPx3 as a biomarker for CMD, particularly in T2DM, and the lack of a significant decline in GPx3 levels in prediabetic individuals suggests that it may not serve reliably as an early indicator of CMDs, warranting further large-scale validation.

Targeted serum proteomics of longitudinal samples from newly diagnosed youth with type 1 diabetes distinguishes markers of disease and C-peptide trajectory

Aims/hypothesisThere is a growing need for markers that could help indicate the decline in beta cell function and recognise the need and efficacy of intervention in type 1 diabetes. Measurements of suitably selected serum markers could potentially provide a non-invasive and easily applicable solution to this challenge. Accordingly, we evaluated a broad panel of proteins previously associated with type 1 diabetes in serum from newly diagnosed individuals during the first year from diagnosis. To uncover associations with beta cell function, comparisons were made between these targeted proteomics measurements and changes in fasting C-peptide levels. To further distinguish proteins linked with the disease status, comparisons were made with measurements of the protein targets in age- and sex-matched autoantibody-negative unaffected family members (UFMs).MethodsSelected reaction monitoring (SRM) mass spectrometry analyses of serum, targeting 85 type 1 diabetes-associated proteins, were made. Sera from individuals diagnosed under 18 years (n=86) were drawn within 6 weeks of diagnosis and at 3, 6 and 12 months afterwards (288 samples in total). The SRM data were compared with fasting C-peptide/glucose data, which was interpreted as a measure of beta cell function. The protein data were further compared with cross-sectional SRM measurements from UFMs (n=194).ResultsEleven proteins had statistically significant associations with fasting C-peptide/glucose. Of these, apolipoprotein L1 and glutathione peroxidase 3 (GPX3) displayed the strongest positive and inverse associations, respectively. Changes in GPX3 levels during the first year after diagnosis indicated future fasting C-peptide/glucose levels. In addition, differences in the levels of 13 proteins were observed between the individuals with type 1 diabetes and the matched UFMs. These included GPX3, transthyretin, prothrombin, apolipoprotein C1 and members of the IGF family.Conclusions/interpretationThe association of several targeted proteins with fasting C-peptide/glucose levels in the first year after diagnosis suggests their connection with the underlying changes accompanying alterations in beta cell function in type 1 diabetes. Moreover, the direction of change in GPX3 during the first year was indicative of subsequent fasting C-peptide/glucose levels, and supports further investigation of this and other serum protein measurements in future studies of beta cell function in type 1 diabetes.Graphical

Selenium level correlates negatively with antibodies but positively with thyroid function in children with down syndrome: an Indonesian study.

Children with Down syndrome (DS) are prone to developing autoimmune thyroid disease (AITD). Previous studies found lower selenium (Se) levels in children with AITD. Glutathione peroxidase-3 (GPx3) and selenoprotein-P (SePP) are widely used to measure Se levels. DS children tend to have lower Se levels, the main contributor to hypothyroidism in this population. This study aimed to analyze the Se's role in AITD in Indonesian children with DS. This cross-sectional study was conducted between February 2021-June 2022 at the Pediatric Outpatient Clinic of Dr Soetomo Hospital. DS children aged 1 month to 18 years were enrolled using consecutive sampling. Thyroid-stimulating hormone, free thyroxine, thyroid peroxidase (TPO-Ab) and thyroglobulin (Tg-Ab) autoantibody, GPx3, and SePP levels were measured in plasma samples using enzyme-linked immunosorbent assays. Statistical analyses used Chi-square, Mann-Whitney, and Spearman's rank correlation (r s). All results with p<0.05 were considered statistically significant. Among 62 children with DS, SePP and GPx3 levels were significantly lower in those with AITD than those without AITD (p=0.013 and p=0.018, respectively). SePP and GPx3 levels correlated significantly with lower TPO-Ab (r s=-0.439 with p=1×10-5 and r s=-0.396 with p=0.001, respectively) and Tg-Ab (r s=-0.474 with p=1×10-5 and r s=-0.410 with p=0.001, respectively) levels. SePP levels correlated significantly with lower thyroid dysfunction incidence (r s=-0.252, p=0.048) in the AITD group. Selenium deficiency contributes to autoimmune process in the thyroid and to thyroid dysfunction in children with Down syndrome. Our findings recommend increasing Se levels through Se-containing foods to reduce the risks of AITD and thyroid dysfunction in DS children with AITD.

Prognostic value and immunological roles of GPX3 in gastric cancer.

Objective: The prognosis for gastric cancer (GC), a prevalent tumor of the digestive system, is unfavorable. The involvement of glutathione peroxidase 3 (GPX3) in tumorigenesis is significant, yet its specific role in GC remains insufficiently investigated. Thus, the aim of this study was to determine the potential impact of GPX3 on GC and elucidate the underlying mechanism. Methods: The expression and survival of GPX3 in GC were analyzed using TCGA data. Additionally, the GPX3 mRNA and protein levels in GC were also assessed using datasets from GTEx, GEPIA, and HPA. A total of 38 pairs of GC tissues, along with their adjacent normal tissues, were collected from the Tianjin Medical University General Hospital, accompanied by detailed clinical information. The expression levels of GPX3 were subsequently determined for the purpose of validation. Following expression, correlation, and survival analyses, we proceeded to investigate the upstream non-coding RNA (ncRNA) of GPX3 using starBase and miRNet. Additionally, the co-expression networks of GPX3 were examined based on LinkedOmics. Lastly, we explored the correlation between GPX3 and immune cell infiltration, as well as the biomarkers of immune cells and immune checkpoints in GC. Furthermore, the GDSC database offered valuable drug sensitivity information. Results: A lower expression of GPX3 was observed in individuals with GC, while a higher expression of GPX3 was associated with a poorer prognosis. The DUBR/hsa-miR-502-3p/GPX3 pathway was identified as the most promising upstream ncRNA pathway related to GPX3 in GC. GO and KEGG enrichment analysis revealed that GPX3 expression was linked to coagulation cascades and cell locomotion. Furthermore, GPX3 levels in GC were positively correlated with immune cell infiltration, immune cell biomarkers, and immune checkpoint expression. The group with low GPX3 expression also exhibited increased sensitivity to 5-fluorouracil, doxorubicin, and other drugs. Conclusions: Collectively, we hypothesized that the potential involvement of non-coding RNAs in the downregulation of GPX3 could contribute to the inhibition of tumor formation during the malignant transition from gastritis to GC. Nevertheless, it was plausible that GPX3 may also facilitate tumor progression to advanced stages by promoting immune cell infiltration and activating immune checkpoints.

Elevated Selenoprotein P Levels in Thalassemia Major Patients

Previous studies have measured selenium levels and glutathione peroxidase 3 (GPX3) activity in patients with thalassemia major (TM). However, Selenoprotein P (SEPP), which is responsible for the storage and transport of selenium, has not been studied in thalassemia patients. This study aims to correlate thyroid functions of TM patients with their SEPP and GPX3 levels. Eighty subjects (40 controls, 40 TM patients) were included in this study. GPX3 and SEPP concentrations were measured in all subjects using sandwich ELISA. Iron, ferritin, urinary iodine, thyroxine (T4), triiodothyronine (T3), thyrotropin (TSH), anti-thyroid peroxidase (anti-TPO), and anti-human thyroglobulin (anti-hTG) concentrations were also measured. Mean SEPP concentration was higher in the TM group compared to the control group. A slight elevation in GPX3 levels was also observed in thalassemia patients, yet it was not statistically significant. In both TM patients and controls, ferritin was inversely correlated with free T4 concentration and GPX3 was inversely correlated with free T4 and T3 concentrations. There was also a negative correlation between SEPP and TSH concentrations in healthy subjects. This is the first study, which has measured SEPP concentrations in thalassemia patients. SEPP levels were higher in TM patients compared to controls. Correlations between thyroid hormones and selenoproteins may indicate that selenium is necessary for thyroid function. Detailed studies are required to elaborate the role of SEPP in thyroid metabolism in thalassemia patients.

Selenoprotein Gene mRNA Expression Evaluation During Renal Ischemia-Reperfusion Injury in Rats and Ebselen Intervention Effects.

Effects of selenoproteins on many renal diseases have been reported. However, their role in renal ischemia-reperfusion (I/R) injury is unclear. The present study was performed to investigate the impact of ebselen and renal I/R injury on the expression of selenoproteins. Sprague-Dawley rats were pretreated with or without ebselen (10mg/kg) through a daily single oral administration from 3days before renal I/R surgery. RT-qPCR (real-time quantitative PCR) was performed to determine the mRNA expression of 25 selenoprotein genes in the renal tissues. The expression levels of two selenoproteins, including GPX3 (glutathione peroxidase 3) and DIO1 (iodothyronine deiodinase 1), were evaluated by Western blot or/and IHF (immunohistofluorescence) assays. Furthermore, renal function, renal damage, oxidative stress, and apoptosis were assessed. The results showed that in renal I/R injury, the mRNA levels of 15 selenoprotein genes (GPX1, GPX3, GPX4, DIO1, DIO2, TXNRD2, TXNRD3, SEPHS2, MSRB1, SELENOF, SELENOK, SELENOO, SELENOP, SELENOS, and SELENOT) were decreased, whereas those of eight selenoprotein genes (GPX2, GPX6, DIO3, TXNRD1, SELENOH, SELENOM, SELENOV, and SELENOW) were increased. I/R also induced a reduction in the expression levels of GPX3 and DIO1 proteins. In addition, our results indicated that ebselen reversed the changes in those selenoprotein genes, excluding SELENOH, SELENOM, SELENOP, and SELENOT, in renal I/R injury and alleviated I/R-induced renal dysfunction, tissue damage, oxidative stress, and apoptosis. To our knowledge, this is the first study to investigate the changes of 25 mammalian selenoprotein genes in renal I/R injury kidneys. The present study also provided more evidence for the roles of ebselen against renal I/R injury.

Glutathione peroxidase 3 (extracellular isoform) levels and functional polymorphisms in fertile and infertile men

BackgroundOxidative stress has an undeniable role in the impairment of sperm function and idiopathic male infertility. On the other hand, the local antioxidant system particularly glutathione peroxidase 3 (GPX3) as an extracellular enzyme protects male fertility from oxidative damages. Therefore, in the current study, we evaluated the association between two functional polymorphisms of the GPX3 gene with its levels in seminal fluid and subsequently with the risk of male infertility.ResultWe recruited 100 fertile and 100 infertile men for the study. Our results showed that the concentration of GPX3 was higher in the fertile group than infertile patients (p= <0.01), and there were positive correlations between GPX3 concentration in seminal fluid with sperm motility and morphology. The frequency of rs8177404 and rs3828599 genotypes and alleles was significantly different between the groups and we found that having the rs8177404 polymorphism (TC and CC genotypes) could increase the risk of idiopathic infertility more than 2-fold. On the other hand, the GG genotype (rs3828599) showed a protective effect against infertility. Our results demonstrated that men carrying CC genotype of rs8177404 polymorphism had significantly lower progressively motile sperm and higher immotile sperm compared with subjects carrying TT and TC genotypes. In the rs3828599 polymorphism, the GG carriers had significantly higher progressively motile and lower immotile sperm than AA carriers. Furthermore, men with genotypes of CC (rs8177404) and GG (rs3828599) had significantly lower and higher levels of GPX3 in the seminal fluid, respectively.ConclusionIn conclusion, our results showed associations between sperm parameters with GPX3 levels and the gene polymorphisms. It seems rs8177404 and rs3828599 polymorphisms can affect GPX3 levels in seminal fluid and subsequently sperm parameters.

Glutathione Peroxidase 3 as a Biomarker of Recurrence after Lung Cancer Surgery.

We aimed to examine the usefulness of serum glutathione peroxidase 3 (GPx3) as a biomarker of lung cancer recurrence after complete resection. We prospectively collected serial serum samples at the baseline, as well as 3, 6 and 12 months after surgery from complete resection cases in 2013. GPx3 levels were measured by enzyme-linked immunosorbent assay. Statistical tests including t-tests and Cox proportional hazard regression analyses were performed. Totally, 135 patients were enrolled, and 39 (28.9%) showed relapse during the median follow-up period (63.60 months; range, 0.167–81.867). The mean GPx3 change was significantly higher in the recurrence group at 6 months (0.32 ± 0.38 vs. 0.15 ± 0.29, p = 0.016) and 12 months (0.40 ± 0.37 vs. 0.13 ± 0.28, p = 0.001). The high GPx3 change group showed significantly higher 60-months recurrence rates than the low group (48.1% vs. 25.2% at 3 months, p = 0.005; 54.5% vs. 28.9% at 6 months, p = 0.018; 38.3% vs. 18.3% at 12 months, p = 0.035). High GPx3 change at 3 months were independent risk factors of recurrence (hazard ratio (HR) 3.318, 95% confidence interval (CI), 1.582–6.960, p = 0.002) and survival (HR 3.150, 95% CI, 1.301–7.628, p = 0.011). Therefore, serum GPx3 changes after surgery may be useful predictive biomarkers for recurrence in lung cancer. Larger-scale validation studies are warranted to confirm these findings.

Beneficial antioxidant status of piglets from sows fed selenomethionine compared with piglets from sows fed sodium selenite

BackgroundStudies in mammals proved dietary organic selenium (Se) being superior to inorganic Se regarding effects on growth performance, antioxidative status, immune response, and Se homeostasis. However, the picture of possible effects of different Se sources and – levels can be expanded. The present field study evaluated the effects on weight gain, hematological and selected biochemical variables as well as plasma concentrations of vitamin E (vitE), total Se and selenobiomolecules in piglets throughout the suckling period. MethodsPiglets were monitored from birth to 38 days of age (d). The mother sows’ diets were enriched with l-selenomethionine (SeMet-0.26 and -0.43 mg Se/kg feed) or sodium selenite (NaSe-0.40 and -0.60 mg Se/kg feed) from 1 month prior to farrowing until the end of lactation period. Piglets received pelleted feed supplemented with Se similarly to the sows’ diets from one week of age. Selenite at 0.40 mg Se/kg (NaSe-0.40) represents a common Se source and -level in pig feed and served as control diet. ResultsFrom 24d, piglets in SeMet-groups had higher mean body weight (BW) compared with piglets from sows fed NaSe-0.40. Furthermore, from five-d and above, piglets from sows fed NaSe-0.60 had significantly higher BW than offspring from sows fed NaSe-0.40. Neonatal piglets in group SeMet-0.43 had significantly lower red blood cell counts (RBC), hemoglobin (Hgb) and hematocrit (Hct) concentrations compared with piglets from sows fed with NaSe-0.40. Neonatal and 5d-old piglets in group SeMet-0.26 showed higher gamma-glutamyl transferase activity than piglets in group NaSe-0.40. From five d and above, group NaSe-0.60 excelled with increased specific hematological variables culminating at age 38d with increased Hct, mean corpuscular volume (MCV), and MC hemoglobin (MCH) as well as increased activities of aspartate transaminase and lactate dehydrogenase compared with the other groups. Generally, offspring in the SeMet groups had higher total Se-concentrations in plasma than those from sows fed selenite, and showed a dose-response effect on plasma Se-concentrations. Furthermore, SeMet-fed piglets had higher plasma levels of the selenoproteins (Sel) glutathione peroxidase 3 (GPx3) and SelP as well as selenoalbumin. Plasma vitE levels were significantly negatively correlated with RBC throughout trial period. ConclusionsMaternal supplementation with SeMet during gestation influenced hematology and clinical biochemistry in neonatal piglets in a different way than in offspring from sows receiving selenite enriched diets. Growth performance was positively influenced by both dietary Se source and Se level. Higher plasma levels of GPx3 observed in piglets receiving SeMet probably improved the protection against birth or growth related oxidative stress. These might prime the piglets for demanding situations as indicated by higher weight gain in offspring from sows fed with SeMet-supplemented diets. Our results on some enzyme activities might indicate that piglets fed NaSe-0.60 had to cope with increased levels of oxidative stress compared with those originating from sows fed SeMet or lower dietary levels of selenite. We assume that combining inorganic and organic Se sources in complete feed for breeding sows might be beneficial fro reproduction and the offspring’s performance.

Troglitazone inhibits the migration and invasion of PC-3 human prostate cancer cells by upregulating E-cadherin and glutathione peroxidase 3.

Troglitazone (TGZ) is a synthetic peroxisome proliferator-activated receptor γ (PPARγ) ligand that exhibits potential antitumor effects on a number of cancer subtypes, including prostate cancer. However, little is known about the effect of TGZ on metastasis in prostate cancer. The aim of the present study was to determine the inhibitory effect and mechanism underlying TGZ on cell growth, migration and invasion using the prostate cancer PC-3 cell line. Cellular migration and invasion were evaluated by performing a wound healing assay and Matrigel assay, respectively. The expression levels of mRNA and protein were determined by reverse transcription-quantitative polymerase chain reaction and western blotting. The results demonstrated that TGZ dose-dependently inhibited cell migration and invasion of PC-3 cells. The present study also revealed that TGZ increased the mRNA and protein levels of E-cadherin and glutathione peroxidase 3 (GPx3) in human prostate cancer PC-3 cells. In addition, GW9662, a PPARγ antagonist, attenuated the increased mRNA and protein levels of E-cadherin and GPx3, suggesting that the PPARγ-dependent signaling pathway was involved. Taken together, these results suggested that the anti-migration and anti-invasion effect of TGZ on PC-3 prostate cancer cells is, at least in part, mediated via upregulation of E-cadherin and GPx3. The present study also concluded that PPARγ may be used as a potential remedial target for the prevention and treatment of prostate cancer cell invasion and metastasis.

Role of hepcidin in hearing loss

Background: Hearing loss is considered as a public health problem that affects the population at all ages. Hepcidin is an important protein with a crucial role in the homeostasis and metabolism of iron. Objective: The objective of this study was to evaluate the association between hepcidin and hearing loss and to find out the mechanisms that lead to this association. Materials and Methods: A total of 300 persons included in this study, 150 as a patients' group who are suffering from hearing loss and attended Al-Sadder Teaching Hospital in Al-Najaf Al-Ashraf City, Iraq, while the other 150 participants who are selected randomly as controls' group and are free from hearing loss. The ages of all participants ranged between 18 and 70 years, and controls were matched with patients by gender and age (within 5 years). Many parameters are measured such as hepcidin, C-reactive protein (CRP), interleukin-6 (IL-6), advanced glycation end products (AGEs), and glutathione peroxidase-3 (GPX-3). Results: The results of this study revealed that sensorineural hearing loss was the most common type followed by mixed one. Furthermore, it was shown that hepcidin and CRP were significantly higher in patients compared with controls, while there were no significant differences between patients and controls in the levels of IL-6, AGEs, and GPX-3. The correlation analyses showed a significant positive correlation between hepcidin and CRP and hepcidin and IL-6. Conclusion: Hepcidin and CRP have a negative impact on hearing, increase significantly with hearing loss, and have role in the development of hearing loss.

Is There an Interplay Between Adherence to Mediterranean Diet, Antioxidant Status, and Vascular Disease in Atrial Fibrillation Patients?

Mediterranean Diet (Med-Diet) is associated with reduced incidence of vascular events (VEs) in atrial fibrillation (AF), but the mechanism accounting for its beneficial effect is only partially known. We hypothesized that Med-Diet may reduce VEs by improving antioxidant status, as assessed by glutathione peroxidase 3 (GPx3) and superoxide dismutase (SOD). We performed a prospective cohort study investigating the relationship between adherence to Med-Diet, serum baseline GPx3 and SOD activities, and the occurrence of VEs in 690 AF patients. GPx3 activity was directly associated with Med-Diet score (B = 0.192, p < 0.001) and inversely with age (B = -0.124, p = 0.001), after adjustment for potential confounders; Med-Diet weakly affected SOD levels. During a mean follow-up of 46.1 ± 28.2 months, 89 VEs were recorded; patients with VEs had lower GPx3 levels compared with those without VEs (p = 0.002); and no differences regarding SOD activity were found. Multivariable Cox regression analysis showed that age (Hazard ratio [HR]:1.065, p < 0.001), logGPx3 (above median, HR: 0.629, p < 0.05), and Med-Diet score (HR: 0.547, p < 0.05) predicted VEs. Med-Diet favorably modulates antioxidant activity of GPx3 in AF, resulting in reduced VEs rate. We hypothesize that the modulation of GPx3 levels by Med-Diet could represent an additional nutritional strategy to prevent VEs in AF patients. Antioxid. Redox Signal. 25, 751-755.

Glutathione peroxidase 3 localizes to the epithelial lining fluid and the extracellular matrix in interstitial lung disease.

Aberrant antioxidant activity and excessive deposition of extracellular matrix (ECM) are hallmarks of interstitial lung diseases (ILD). It is known that oxidative stress alters the ECM, but extracellular antioxidant defence mechanisms in ILD are incompletely understood. Here, we extracted abundance and detergent solubility of extracellular antioxidant enzymes from a proteomic dataset of bleomycin-induced lung fibrosis in mice and assessed regulation and distribution of glutathione peroxidase 3 (GPX3) in murine and human lung fibrosis. Superoxide dismutase 3 (Sod3), Gpx3, and Gpx activity were increased in mouse BALF during bleomycin-induced lung fibrosis. In lung tissue homogenates, Gpx3, but not Sod3, was upregulated and detergent solubility profiling indicated that Gpx3 associated with ECM proteins. Immunofluorescence analysis showed that Gpx3 was expressed by bronchial epithelial cells and interstitial fibroblasts and localized to the basement membrane and interstitial ECM in lung tissue. As to human ILD samples, BALF of some patients contained high levels of GPX3, and GPX3 was upregulated in lung homogenates from IPF patients. GPX3 expression in primary human bronchial epithelial cells and lung fibroblasts was downregulated by TNF-α, but more variably regulated by TGF-β1 and menadione. In conclusion, the antioxidant enzyme GPX3 localizes to lung ECM and is variably upregulated in ILD.

The biological impact of e-cigarettes on airway epithelial cell transformation and gene expression

Background: Glutathione peroxidase 3 (GPx3) which is an extracellular secretory protein is down regulated in patients with early stage lung cancer. We examined the usefulness of serum GPx3 as a biomarker for monitoring of relapse after surgery. Methods: We prospectively collected serial serum samples at baseline, 3 months (3m), 6 months (6m), and 12 months (12m) after operation from the patients who underwent surgery during the year 2013. GPx3 levels were measured three times per sample using the enzyme-linked immunosorbent assay, and the mean values were analyzed by t-test and paired t-test. Results: A total of 170 (100 adenocarcinoma, 41 squamous cell carcinoma, 29 others) patients were analyzed in this study. Mean age was 64.1 years old (range, 39-80) and 27 (15.9%) out of 165 lung cancer patients were confirmed relapse during the median follow-up period of 597.5 days (range, 5-938). The mean GPx3 value at postoperative 6m was significantly elevated in relapsed group than control group (7.90 ± 2.44 mg/mL vs. 6.99 ± 1.79 mg/mL, p1⁄40.047). The mean GPx3 differences were significantly higher in relapsed group than control group at 3m (-0.38 ± 0.39 mg/mL vs. -0.21 ± 0.36 mg/mL, p1⁄40.044), 6m (-0.37 ± 0.42 mg/mL vs. -0.19 ± 0.30 mg/mL, p1⁄40.024), and 12m (-0.38 ± 0.42 mg/mL vs. -0.19 ± 0.28 mg/mL, p1⁄40.012). The mean time to relapse was significantly shorter in high level of GPx3 group at postoperative 3m (694.83 ± 31.86 days vs. 839.05 ± 24.31 days, p1⁄40.007). The mean time to relapse was significantly shorter in high GPx3 difference group between baseline and postoperative 3m (729.76 ± 34.89 days vs. 838.18 ± 24.03 days, p1⁄40.002). Conclusion: Serum mean GPx3 value at postoperative 6m and the mean GPx3 difference were significantly elevated in relapsed lung cancer. The mean time to relapse was significantly shorter in high level of GPx3 group at postoperative 3m. More large scaled validation studies are warranted.

Serum glutathione peroxidase 3 as a biomarker of postoperative relapse in patients with lung cancer

Background: Glutathione peroxidase 3 (GPx3) which is an extracellular secretory protein is down regulated in patients with early stage lung cancer. We examined the usefulness of serum GPx3 as a biomarker for monitoring of relapse after surgery. Methods: We prospectively collected serial serum samples at baseline, 3 months (3m), 6 months (6m), and 12 months (12m) after operation from the patients who underwent surgery during the year 2013. GPx3 levels were measured three times per sample using the enzyme-linked immunosorbent assay, and the mean values were analyzed by t-test and paired t-test. Results: A total of 170 (100 adenocarcinoma, 41 squamous cell carcinoma, 29 others) patients were analyzed in this study. Mean age was 64.1 years old (range, 39-80) and 27 (15.9%) out of 165 lung cancer patients were confirmed relapse during the median follow-up period of 597.5 days (range, 5-938). The mean GPx3 value at postoperative 6m was significantly elevated in relapsed group than control group (7.90 ± 2.44 mg/mL vs. 6.99 ± 1.79 mg/mL, p1⁄40.047). The mean GPx3 differences were significantly higher in relapsed group than control group at 3m (-0.38 ± 0.39 mg/mL vs. -0.21 ± 0.36 mg/mL, p1⁄40.044), 6m (-0.37 ± 0.42 mg/mL vs. -0.19 ± 0.30 mg/mL, p1⁄40.024), and 12m (-0.38 ± 0.42 mg/mL vs. -0.19 ± 0.28 mg/mL, p1⁄40.012). The mean time to relapse was significantly shorter in high level of GPx3 group at postoperative 3m (694.83 ± 31.86 days vs. 839.05 ± 24.31 days, p1⁄40.007). The mean time to relapse was significantly shorter in high GPx3 difference group between baseline and postoperative 3m (729.76 ± 34.89 days vs. 838.18 ± 24.03 days, p1⁄40.002). Conclusion: Serum mean GPx3 value at postoperative 6m and the mean GPx3 difference were significantly elevated in relapsed lung cancer. The mean time to relapse was significantly shorter in high level of GPx3 group at postoperative 3m. More large scaled validation studies are warranted.

Reactive Oxygen Species and Serous Epithelial Ovarian Adenocarcinoma.

Serous ovarian cancer (SOC) is usually diagnosed at late stage and stage-adjusted five year survival rate is low. Mortality is relatively heavy on African-Americans/Black (AA) affected with SOC compared to their Caucasian counterparts, though the cause for the disparity remains unclear. DNA damage induced by oxidative stress has been linked to ovarian cancer, but the role of oxidative stress in distinguishing differences in aggressive SOC tumors among patients is yet to be determined. This study aims to determine the levels of reactive oxygen species (ROS), malondialdehyde (MDA), reactive carbonyl groups and antioxidants in primary SOC normal, precancerous (cystadenoma, borderline) and invasive (III/IV) tissue samples obtained from AA and Caucasian subgroups. Additionally, the study seeks to investigate significant changes in the level of ROS between AA and Caucasian SOC samples. A fluorogenic probe, dichlorodihydrofluorescein (DCFH-DiOxyQ), was used to scavenge reactive oxygen species in SOC normal, precancerous and malignant stages III/IV tissue samples. Malondialdehyde (MDA), a lipid peroxidation marker, and reactive carbonyl groups were measured as indicators of oxidative injury. Moreover, antioxidant status was assessed by estimating glutathione peroxidase 3 (GPX3) enzyme levels. Results indicate ROS concentration was approximately 96% higher in the malignant tissues in comparative to the normal non-diseased controls. In addition, ROS concentration among AA women was approximately 9% higher than Caucasian women. MDA levels increased exponentially from non-disease control and precancerous tissues relative to malignant tissues. Furthermore, malignant serous ovarian samples showed significantly higher reactive carbonyl content compared to the non-disease controls (p=0.009), while GPX3 levels decreased considerably in serous cystadenoma and malignant tissue samples, and non-diseased control compared to borderline disease. The results suggest accumulation of ROS and MDA levels may be a causative factor for SOC. Elevated levels of MDA and reactive carbonyl proteins could override the GPX3 enzyme capacity therefore, initiating serous ovarian neoplasm.

Alteration in the intrafollicular thiol-redox system in infertile women with endometriosis.

The aim of this study was to compare intrafollicular biomarkers of thiol-redox system and chronic inflammation in infertile patients with and without endometriosis, and examine correlations between biomarkers and IVF outcomes. The study included 65 patients receiving IVF: 31 patients with endometriosis vs 34 patients without endometriosis. Follicular fluid (FF) was obtained from a single-dominant follicle during oocyte retrieval and stored at -70 °C. Malondialdehyde, superoxide dismutase, glutathione (GSH), glutathione peroxidase 3 (GPX3), thioredoxin (TRX), TRX-binding protein 2 (TBP2), and peroxiredoxin-4 levels were measured in the FF samples by ELISAs as biomarkers of oxidative stress. The inflammatory cytokines interleukin 1 beta (IL1β), IL6, IL8, and tumor-necrosis factor alpha (TNFα) were also measured by ELISAs. GSH levels were significantly lower in the endometriosis group compared with the controls. TBP2 levels were significantly higher in the endometriosis group. IL6, IL8, and TNFα levels were significantly higher in the endometriosis group. The levels of all of the inflammatory cytokines positively correlated with the levels of TRX. GSH levels positively correlated with the number of high-quality embryos. GPX3 and TRX levels negatively correlated with the percentage of mature oocytes. TNFα levels negatively correlated with the cumulative embryo score per embryo. Logistic regression analysis revealed that the number of high-quality embryos was an independent factor predicting clinical pregnancy. In conclusion, there may be an imbalance in the thiol-redox system and increased levels of inflammatory cytokines in the intrafollicular microenvironment of infertile patients with endometriosis, which may affect the qualities of the oocyte and embryo.