Serum Glutathione Peroxidase 3 Research Articles

Selenium status and its determinants in very old adults: insights from the Newcastle 85+ Study.

There is a dearth of data on Se status in very old adults. The aims of this study were to assess Se status and its determinants in 85-year-olds living in the Northeast of England by measuring serum Se and selenoprotein P (SELENOP) concentrations and glutathione peroxidase 3 (GPx3) activity. A secondary aim was to examine the interrelationships between each of the biomarkers. In total, 757 participants (463 women, 293 men) from the Newcastle 85+ Study were included. Biomarker concentrations were compared with selected cut-offs (serum Se: suboptimal 70 µg/l and deficient 45 µg/l; SELENOP: suboptimal 4·5 mg/l and deficient 2·6 mg/l). Determinants were assessed using linear regressions, and interrelationships were assessed using restricted cubic splines. Median (inter-quartile range) concentrations of serum Se, SELENOP and of GPx3 activity were 53·6 (23·6) µg/l, 2·9 (1·9) mg/l and 142·1 (50·7) U/l, respectively. Eighty-two percentage and 83 % of participants had suboptimal serum Se (< 70 µg/l) and SELENOP (< 4·5 mg/l), and 31 % and 40 % of participants had deficient serum Se (< 45 µg/l) and SELENOP (< 2·6 mg/l), respectively. Protein intake was a significant determinant of Se status. Additional determinants of serum Se were sex, waist:hip ratio, self-rated health and disease, while sex, BMI and physical activity were determinants of GPx3 activity. There was a linear association between serum Se and SELENOP, and nonlinear associations between serum Se and GPx3 activity and between SELENOP and GPx3 activity. These findings indicate that most participants had suboptimal Se status to saturate circulating SELENOP.

The Association Between Serum Glutathione Peroxidase-3 Concentration and Risk of Acute Kidney Injury After Cardiac Surgery: A Nested Case-Control Study

Oxidative stress has an integral role in the pathophysiology of cardiac surgery-associated acute kidney injury (CSA-AKI). Glutathione peroxidase 3 (GPx3) is an important antioxidant enzyme in circulation and is mainly secreted by the kidney. This study aimed to evaluate the relation between GPx3 protein and CSA-AKI. This study is a nested case-control study in Zhongshan Hospital affiliated with Fudan University. We examined serum samples from 80 CSA-AKI patients and 80 age- and gender-matched non-AKI patients who underwent cardiac surgery. AKI was defined according to Kidney Disease: Improving Global Outcomes (KDIGO) 2012 criteria. We measured serum GPx3 concentration using the enzyme-linked immunosorbent assay. GPx3 ratio is the ratio of preoperative and 6hours postoperative of GPx3 protein concentration. We applied dose-response relation analyses to odds ratio in different GPx3 ratio levels and integrated it into the logistic model to predict the risk of AKI. The receiver operating characteristic curve and area under the curve (AUC) was used to assess the prediction models. Postoperative serum GPx3 concentrations were significantly lower in the AKI group compared with the non-AKI group (1.78±0.33 vs 2.03±0.27, p<0.001). Malondialdehyde was higher in the AKI than in the non-AKI group (17.74±8.65 vs 7.48±4.59, p<0.001). The AKI risk increased in a dose-dependent manner, which was flat in the first half of the GPx3 ratio and then tended to be faster. The peaking odds ratio of CSA-AKI was 2.615 at the GPx3 ratio of 1.21 to 1.40. The AUC value to predict CSA-AKI only included the GPx3 ratio was 72.3%. After gradually integrating other covariates (body mass index, aortic crossclamp time, and cardiopulmonary bypass), the model showed an AUC of 82.6%. The serum GPx3 concentration was significantly lower in the CSA-AKI group. GPx3 ratio has a good predictive value for CSA-AKI, which may be a potential early diagnostic marker for AKI.

Natural Autoimmunity to Selenoprotein P Impairs Selenium Transport in Hashimoto's Thyroiditis.

The essential trace element selenium (Se) is needed for the biosynthesis of selenocysteine-containing selenoproteins, including the secreted enzyme glutathione peroxidase 3 (GPX3) and the Se-transporter selenoprotein P (SELENOP). Both are found in blood and thyroid colloid, where they serve protective functions. Serum SELENOP derives mainly from hepatocytes, whereas the kidney contributes most serum GPX3. Studies using transgenic mice indicated that renal GPX3 biosynthesis depends on Se supply by hepatic SELENOP, which is produced in protein variants with varying Se contents. Low Se status is an established risk factor for autoimmune thyroid disease, and thyroid autoimmunity generates novel autoantigens. We hypothesized that natural autoantibodies to SELENOP are prevalent in thyroid patients, impair Se transport, and negatively affect GPX3 biosynthesis. Using a newly established quantitative immunoassay, SELENOP autoantibodies were particularly prevalent in Hashimoto’s thyroiditis as compared with healthy control subjects (6.6% versus 0.3%). Serum samples rich in SELENOP autoantibodies displayed relatively high total Se and SELENOP concentrations in comparison with autoantibody-negative samples ([Se]; 85.3 vs. 77.1 µg/L, p = 0.0178, and [SELENOP]; 5.1 vs. 3.5 mg/L, p = 0.001), while GPX3 activity was low and correlated inversely to SELENOP autoantibody concentrations. In renal cells in culture, antibodies to SELENOP inhibited Se uptake. Our results indicate an impairment of SELENOP-dependent Se transport by natural SELENOP autoantibodies, suggesting that the characterization of health risk from Se deficiency may need to include autoimmunity to SELENOP as additional biomarker of Se status.

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.

Association between glutathione peroxidase-3 activity and carotid atherosclerosis in patients with type 2 diabetes mellitus.

Background and AimsDeficiency of glutathione peroxidase 3 (GPx3) has been recognized as an independent risk factor for cardiovascular events. However, little is known regarding the role of GPx3 in carotid atherosclerosis, which is ubiquitously observed in type 2 diabetes mellitus (T2DM). This study aimed to investigate the relationship between GPx3 activity and carotid atherosclerosis among patients with T2DM.MethodsFrom January 2018 to December 2018, 245 consecutive patients with T2DM were enrolled in this observational study. Assessment of serum GPx3 activity was performed after admission. We also used carotid ultrasound to measure the mean carotid intima–media thickness (CIMT) and to assess the presence of carotid plaque.ResultsOf the 245 patients, the median serum GPx3 activity was 22.5 U/ml (interquartile range, 12.4–35.9 U/ml). Carotid plaque was observed in 113 (46.1%) patients, and mean CIMT was 0.8 ± 0.1 mm. Univariate analysis showed that age, smoking, previous coronary heart disease, carotid plaque, and level of mean CIMT and hypersensitive C‐reactive protein were significantly associated with decreasing tertile of GPx3. Furthermore, after adjusting for all potential confounders by multivariable logistic regression analysis, PGx3 activity was significantly and independently associated with the mean CIMT (β = −.406, p = .002) and carotid plaque (first tertile of GPx3, odds ratio, 1.870, 95% confidence intervals, 1.124–3.669, p = .024).ConclusionsThis study demonstrated that serum GPx3 activity was inversely associated with mean CIMT and carotid plaque, suggesting that lower GPx3 activity may be an independent predictor for carotid atherosclerosis in T2DM.

Antioxidant reserve of the lungs and ventilator-associated pneumonia: A clinical trial of high dose selenium in critically ill patients

PurposeTo evaluate the effect of supplemental selenium administration on the incidence of ventilator-associated pneumonia (VAP) in critically ill patients. MethodsNinety-nine mechanically ventilated patients were randomized to receive either selenium or isotonic saline infusion for 10days. The primary endpoint was serum glutathione peroxidase-3 (GPX-3) activity and secondary endpoints were development of VAP or death, ICU stay and vasopressor requirement. Serum concentrations of selenium and GPX-3 were measured on Day-1, Day-4 and Day-10. Chi Square and log-rank analyses were used for statistical analyses and odds ratios were calculated. ResultsSerum selenium and GPX-3 activity levels increased steadily in the treatment group within 10days (P<0.025), while they remained unchanged in the placebo group. The incidence of VAP was 19.4/1000days of mechanical ventilation in the placebo group while it was 15.8/1000 ventilated days in the treatment group (P=0.250). The risk of VAP or death was similar between the treatments and placebo groups. ConclusionDespite increasing the antioxidant activity, selenium supplementation did not affect the incidence of VAP in critically ill patients. The risk of developing VAP or death within 30days of ICU admission remained the same in the treatment and the controls.

Response

To evaluate the effect of supplemental selenium administration on the incidence of ventilator-associated pneumonia (VAP) in critically ill patients.Ninety-nine mechanically ventilated patients were randomized to receive either selenium or isotonic saline infusion for 10 days. The primary endpoint was serum glutathione peroxidase-3 (GPX-3) activity and secondary endpoints were development of VAP or death, ICU stay and vasopressor requirement. Serum concentrations of selenium and GPX-3 were measured on Day-1, Day-4 and Day-10. Chi Square and log-rank analyses were used for statistical analyses and odds ratios were calculated.Serum selenium and GPX-3 activity levels increased steadily in the treatment group within 10 days (P < 0.025), while they remained unchanged in the placebo group. The incidence of VAP was 19.4/1000 days of mechanical ventilation in the placebo group while it was 15.8/1000 ventilated days in the treatment group (P = 0.250). The risk of VAP or death was similar between the treatments and placebo groups.Despite increasing the antioxidant activity, selenium supplementation did not affect the incidence of VAP in critically ill patients. The risk of developing VAP or death within 30 days of ICU admission remained the same in the treatment and the controls.

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.

Diagnostic value of serum glutathione peroxidase 3 levels in patients with lung cancer.

We selected glutathione peroxidase 3 (GPx3) as a specific candidate that is down regulated in patients with lung cancer. In this study, we examined the diagnostic value of serum GPx3, which is an extracellular protein and readily detectable in blood. We collected serum samples from 342 patients with lung cancer and 126 controls (normal healthy people and patients with benign diseases or other malignancies). We measured serum GPx3 levels using the enzyme-linked immunosorbent assay. Mean serum GPx3 levels were significantly lower in the patient group compared with the control group (10.1 ± 5.0 μg/mL vs. 13.0 ± 5.8 μg/mL, P < 0.001). In addition, mean serum GPx3 levels tended to be lower in the patients without metastasis compared with those with metastasis (9.6 ± 4.5 μg/mL vs. 10.7 ± 5.7 μg/mL, P = 0.051). Furthermore, mean serum GPx3 levels had a significant difference according to initial treatments (P < 0.001). In other words, mean serum GPx3 levels were significantly lower in the surgery group (8.2 ± 4.1 μg/mL) compared with the concurrent chemoradiotherapy (11.5 ± 4.6 μg/mL, P < 0.001), chemotherapy (10.7 ± 5.6 μg/mL, P < 0.001), and supportive care groups (10.9 ± 4.8 μg/mL, P = 0.002). Our results showed that serum GPx3 levels were significantly lower in the patients who underwent surgery, which indicates that the serum may have diagnostic value in patients at an operable stage of lung cancer, rather than those at a locally advanced or metastatic stage.

The diagnostic value of serum glutathione peroxidase 3 levels in patients with early-stage lung cancer.

e22232 Background: We have selected glutathione peroxidase 3 (GPx3) as a specific candidate that is down-regulated in patients with lung cancer. In this study, we examined the diagnostic value of serum GPx3 which is extracellular protein and readily detectable in blood. Methods: We collected serum samples from 342 patients with lung cancer and 126 controls (normal healthy people and patients with benign diseases or other malignancies). We measured serum GPx3 levels using the enzyme-linked immunosorbent assay. Results: Mean serum GPx3 levels were significantly lower in the patient group as compared with the control group (10.1 ± 5.0 mg/mL vs. 13.0 ± 5.8 mg/mL, P<0.001). In addition, mean serum GPx3 levels were significantly lower in the patients without metastasis as compared with those with metastasis (9.6 ± 4.5 mg/mL vs. 10.7 ± 5.7 mg/mL, P=0.051). Furthermore, mean serum GPx3 levels had a significant correlation with initial treatments (P<0.001). In other words, mean serum GPx3 levels were significantly...

Glutathione Peroxidase 3 Serum Levels and GPX3 Gene Polymorphisms in Subjects with Metabolic Syndrome

Glutathione peroxidase 3 (GPx3) plays a main role in removing hydro- and lipoperoxides from the body. Changes in concentration and several single-nucleotide polymorphisms (SNP) at the GPX3 gene have been associated with vascular diseases, but the relationship of GPx3 with metabolic syndrome (MetS) remains unexplored. We undertook this study to determine the association of GPx3 serum levels and several GPX3 SNPs with the presence of MetS in Mexican subjects. Clinical, biochemical, and anthropometric evaluation were conducted in 426 subjects assigned to three groups: control (n = 42); risk group (RG, n = 200), and MetS group (n = 184). Insulin sensitivity (IS) and cardiovascular risk were determined by the QUICKI and TG/HDL-C index, respectively. Serum GPx3 was determined by enzyme immunoassay and polymorphisms within GPX3 gene were identified by nucleotide sequencing. MetS group showed low IS and increased cardiovascular risk with respect to controls as well as higher GPx3 serum levels (172.9 ± 32.2 vs. 145.6 ± 24.8 ng/dL; p <0.05). Only three of the ten GPX3 SNPs screened were polymorphic with two haplotypes observed (CCT and TTA-rs8177404, rs8177406, and rs8177409), indicating tight linkage disequilibrium in this genetic region. No differences for either genotype or allele frequencies among groups were observed, but rs8177409 (allele T) was associated with cardiovascular risk (odds ratio [OR], 4.5; p = 0.0125). This study shows that serum levels of GPx3 are increased in subjects with MetS and that rs8177409 SNP was associated with cardiovascular risk in a Mexican population.

Serum Levels of Glutathione Peroxidase 3 in Overweight and Obese Subjects from Central Mexico

Overweight and obesity are considered complex entities in which there are alterations in the concentration of antioxidant enzymes. It has been reported that glutathione peroxidase 3 (GPx3), an extracellular enzyme involved in the reduction of both hydro- and lipoperoxides, shows changes both in gene expression and protein concentration in animal models for type 2 diabetes (T2D) and obesity, but the variability of GPx3 levels in different human populations and under different health conditions are currently unclear. We undertook this study to determine the GPx3 levels in overweight and obese subjects from central Mexico. Biochemical profile (serum glucose, insulin and lipid profile) and GPx3 concentrations were determined in 28 healthy subjects (control) and 133 subjects who were overweight or obese (OW-OB). The OW-OB group had a higher concentration of triacylglycerides (TAG) compared with the control group (201.2 ± 88.7 vs. 100.3 ± 46.4 mg/dL, p <0.05) and the TAG/high density lipoprotein-cholesterol (HDL-C) index (5.6 ± 2.8 vs. 2.1 ± 1.2, p <0.05), whereas the concentration of HDL-C decreased (38.2 ± 8.7 vs. 50.1 ± 14.5 mg/dL, p <0.05). Serum GPx3 was significantly higher in the OW-OB group than in the control group (175.4 ± 25.4 vs. 143.5 ± 23.1 ng/dL). GPx3 concentration correlated with insulin sensitivity (IS) and the TAG/HDL-C index (Rho = -0.2336 and Rho = 0.2275) (p <0.01). The TAG/HDL-C index and serum GPx3 concentration increased in the OW-OB group. In addition, GPx3 had a significant correlation with IS, weight, and the TAG/HDL-C index.