scholarly journals Oxidative Stress and Related Biomarkers in Gilbert’s Syndrome: A Secondary Analysis of Two Case-Control Studies

Antioxidants ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1474
Author(s):  
Karl-Heinz Wagner ◽  
Nazlisadat Seyed Khoei ◽  
Claudia Anna Hana ◽  
Daniel Doberer ◽  
Rodrig Marculescu ◽  
...  

Bilirubin is an important antioxidant and a modulator of biological functions. However, most of the protection against oxidative stress was shown in vitro or ex vivo. The aim of this case-control study was to investigate whether subjects with Gilbert’s syndrome (GS) experience different levels of lipid and protein oxidation (as well as differences in oxidative stress related markers) compared to healthy controls. GS subjects (n = 119) demonstrated higher serum levels of unconjugated bilirubin (p < 0.001), a lower BMI (p < 0.001), 37% higher antioxidant potential assessed as ferric reducing ability potential (p < 0.001), higher advanced oxidation protein products (p < 0.01) andlower apolipoprotein B (p < 0.05), hs-C-reactive protein (p < 0.05), interleukin 6 (p < 0.001) and interleukin 1 beta (p < 0.05) values compared to healthy controls (n = 119). Furthermore, the resting heart rate was significantly lower in the GS group (p < 0.05). Stronger protective effects for GS subjects were demonstrated in the older subgroup (n = 104, average age 50 years) compared to those of the younger group (n = 134, average age 27 years). Although not all markers related to oxidative stress were different between the groups (e.g., malondialdehyde, homocysteine, oxLDL, and myeloperoxidase; p > 0.05), the observed differences contribute to the explanation of why GS serves as an important protector in the pathogenesis of metabolic, oxidative stress related diseases.

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Anna K. Lundberg ◽  
Rosanna W. S. Chung ◽  
Louise Zeijlon ◽  
Gustav Fernström ◽  
Lena Jonasson

Abstract Background Inflammation and oxidative stress form a vicious circle in atherosclerosis. Oxidative stress can have detrimental effects on T cells. A unique subset of CD4+ T cells, known as regulatory T (Treg) cells, has been associated with atheroprotective effects. Reduced numbers of Treg cells is a consistent finding in patients with chronic coronary syndrome (CCS). However, it is unclear to what extent these cells are sensitive to oxidative stress. In this pilot study, we tested the hypothesis that oxidative stress might be a potential contributor to the Treg cell deficit in CCS patients. Methods Thirty patients with CCS and 24 healthy controls were included. Treg (CD4+CD25+CD127−) and conventional T (CD4+CD25−, Tconv) cells were isolated and treated with increasing doses of H2O2. Intracellular ROS levels and cell death were measured after 2 and 18 h, respectively. The expression of antioxidant genes was measured in freshly isolated Treg and Tconv cells. Also, total antioxidant capacity (TAC) was measured in fresh peripheral blood mononuclear cells, and oxidized (ox) LDL/LDL ratios were determined in plasma. Results At all doses of H2O2, Treg cells accumulated more ROS and exhibited higher rates of death than their Tconv counterparts, p < 0.0001. Treg cells also expressed higher levels of antioxidant genes, including thioredoxin and thioredoxin reductase-1 (p < 0.0001), though without any differences between CCS patients and controls. Tconv cells from CCS patients were, on the other hand, more sensitive to oxidative stress ex vivo and expressed more thioredoxin reductase-1 than Tconv cells from controls, p < 0.05. Also, TAC levels were lower in patients, 0.97 vs 1.53 UAE/100 µg, p = 0.001, while oxLDL/LDL ratios were higher, 29 vs 22, p = 0.006. Conclusion Treg cells isolated from either CCS patients or healthy controls were all highly sensitive to oxidative stress ex vivo. There were signs of oxidant-antioxidant imbalance in CCS patients and we thus assume that oxidative stress may play a role in the reduction of Treg cells in vivo.


2020 ◽  
Author(s):  
Anna K Lundberg ◽  
Rosanna WS Chung ◽  
Louise Zeijlon ◽  
Gustav Fernström ◽  
Lena Jonasson

Abstract BackgroundInflammation and oxidative stress form a vicious circle in atherosclerosis. Oxidative stress can have detrimental effects on T cells. A unique subset of CD4+ T cells, known as regulatory T (Treg) cells, has been associated with atheroprotective effects. Reduced numbers of Treg cells is a consistent finding in patients with chronic coronary syndrome (CCS). However, it is unclear to what extent these cells are sensitive to oxidative stress. In the present study, we tested the hypothesis that oxidative stress might be a potential contributor to the Treg cell deficit in CCS patients. MethodsThirty patients with CCS and 24 healthy controls were included. Treg (CD4+CD25+CD127-) and conventional T (CD4+CD25-, Tconv) cells were isolated and treated with increasing doses of H2O2. Intracellular ROS levels and cell death were measured after 2 and 18 h, respectively. The expression of antioxidant genes was measured in freshly isolated Treg and Tconv cells. Alxo, total antioxidant capacity (TAC) was measured in fresh peripheral blood mononuclear cells. ResultsAt all doses of H2O2, Treg cells accumulated more ROS and exhibited higher rates of death than their Tconv counterparts, p < 0.0001. Treg cells also expressed higher levels of antioxidant genes, including thioredoxin and thioredoxin reductase-1 (p < 0.0001), though without any differences between CCS patients and controls. Tconv cells from CCS patients were, on the other hand, more sensitive to oxidative stress ex vivo and expressed more thioredoxin reductase-1 than Tconv cells from controls, p < 0.05. Also, TAC levels were lower in patients, 0.97 vs 1.53 UAE/100 µg, p = 0.001. ConclusionTreg cells isolated from either CCS patients or healthy controls were all highly sensitive to oxidative stress ex vivo. There were however signs of oxidant-antioxidant imbalance in CCS patients and we thus assume that oxidative stress plays a role in the reduction of Treg cells in vivo.


2011 ◽  
Vol 140 (5) ◽  
pp. S-799 ◽  
Author(s):  
Shireen Ghorbani ◽  
Amir Nejad ◽  
David Law ◽  
Kathleen Chua ◽  
Meridythe M. Amichai ◽  
...  

2018 ◽  
Vol 2018 ◽  
pp. 1-7
Author(s):  
Xhevat Lumi ◽  
Mateja M. Jelen ◽  
Daša Jevšinek Skok ◽  
Emanuela Boštjančič ◽  
Metka Ravnik-Glavač ◽  
...  

The present study investigated the distribution of genotypes within single nucleotide polymorphisms (SNPs) in genes, related to PVR pathogenesis across European subpopulations. Genotype distributions of 42 SNPs among 96 Slovenian healthy controls were investigated and compared to genotype frequencies in 503 European individuals (Ensembl database) and their subpopulations. Furthermore, a case-control status was simulated to evaluate effects of allele frequency changes on statistically significant results in gene-association studies investigating functional polymorphisms. In addition, 96 healthy controls were investigated within 4 SNPs: rs17561 (IL1A), rs2069763 (IL2), rs2229094 (LTA), and rs1800629 (TNF) in comparison to PVR patients. Significant differences (P<0.05) in distribution of genotypes among 96 Slovenian participants and a European population were found in 10 SNPs: rs3024498 (IL10), rs315952 (IL1RN), rs2256965 (LST1), rs2256974 (LST1), rs909253 (LTA), rs2857602 (LTA), rs3138045 (NFKB1A), rs3138056 (NFKB1A), rs7656613 (PDGFRA), and rs1891467 (TGFB2), which additionally showed significant differences in genotype distribution among European subpopulations. This analysis also showed statistically significant differences in genotype distributions between healthy controls and PVR patients in rs17561 of the IL1A gene (OR, 3.00; 95% CI, 0.77–11.75; P=0.036) and in rs1800629 of the TNF gene (OR, 0.48; 95% CI, 0.27–0.87; P=0.014). Furthermore, we have shown that a small change (0.02) in minor allele frequency (MAF) significantly affects the statistical p value in case-control studies. In conclusion, the study showed differences in genotype distributions in healthy populations across different European countries. Differences in distribution of genotypes may have had influenced failed replication results in previous PVR-related SNP-association studies.


Author(s):  
Parul Chopra ◽  
Rajesh Sagar ◽  
Asok Kumar Mukhopadhyay

Introduction: Depression is associated with activation of innate immune response leading to oxidative damage. The 8-isoprostanes and 8-hydroxy-2-deoxyguanosine (8-OHdG) are biomarkers of oxidative damage to lipids and Deoxyribonucleic Acid (DNA), respectively. They have been independently linked to depression. Aim: To study the oxidative stress markers (8-Isoprostanes and 8-OHdG) in subjects with major depression. Materials and Methods: In this observational case-control study 42 cases of depression, 13-25 years of age were recruited from Psychiatry Out Patient Department (OPD) at a tertiary-care hospital in Delhi, India, along with 42 healthy controls. They were assessed clinically and using psychometric evaluation scores, Beck’s Depression Inventory-II (BDI-II) and Hamilton Depression Rating Scale (HAM-D). All 42 subjects were on medication with antidepressants {33/42 with Selective Serotonin Reuptake Inhibitors (SSRI) 8/42 with Tricyclic Antidepressants (TCA) and 1/42 on a combination of both}. Routine laboratory investigations were done. Plasma 8-Isoprostane and serum 8-OHdG concentrations were measured in both cases and controls. The results obtained were analysed using relevant statistical tests on STATA version 11 (StataCorp, 2009). Results: Clinically, all patients had moderate to severe depression. BDI-II and HAM-D scores were raised in all cases as compared to the controls (28.81±5.60 vs 1.62±1.59 for BDI and 20.88±4.67 vs 1.33±1.43 for HAM-D, respectively). The concentration (in depressed vs controls) of plasma 8-Isoprostane (107.70±54.48 pg/mL vs 77.78±60.15 pg/mL) and serum 8-OHdG (2103.03±154 pg/mL vs 2017±164.69 pg/mL) were significantly elevated (p-value <0.05). Though elevated in patients belonging to both genders, showed significant increase of 8-Isoprostane only in females and 8-OHdG only in males as compared to their healthy controls. No correlation of the levels of any of two markers was seen with clinical severity of depression of patients as assessed by BDI. Conclusion: Evidence of oxidative stress to lipids and DNA are present in the peripheral blood. These can be explored further in establishing the biomarkers for diagnosis and prognosis of depression.


2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Seoung-Jin Hong ◽  
Sang Wook Kang ◽  
Su Kang Kim ◽  
Young Sik Kim ◽  
Ju Yeon Ban

Background. Interleukin-1β(IL-1β) plays an important role as a mediator of various inflammatory responses in chronic periodontitis. Several studies have investigated the potential relationship between IL-1βpolymorphism (rs16944) and susceptibility to chronic periodontitis; inflammatory process is involved, but conclusions is still controversial.Objective. The aim of this study was to determine whether the IL-1βpolymorphism (rs16944) is associated with susceptibility to chronic periodontitis.Material and Methods. For the case-control study, 51 patients with chronic periodontitis and 33 healthy control patients were recruited in the study. Genotyping was conducted by direct sequencing. SNPStats and SPSS 18.0 were used for the analysis of genetic data and to evaluate odds ratios, 95% confidence intervals, andPvalues; logistic regression models were used. And to perform meta-analysis, studies about IL-1βpolymorphism (rs16944) and chronic periodontitis were searched in PubMed, Embase, Google Scholar, and Korean Studies Information Service System (KISS) electronic databases until July 2017.Results. In our case-control study, no significant relationship was revealed between IL-1βpolymorphism (rs16944) and chronic periodontitis (P>0.05in each model). When combined with the previous studies in the meta-analysis, the result was not associated with chronic periodontitis in any of the models (CC vs. CT + TT: OR = 0.97, 95% CI = 0.762–1.246; CC + CT vs. TT: OR = 0.90, 95% CI = 0.658–1.232; and C vs. T: OR = 0.93, 95% CI = 0.774–1.128). The subgroup analysis stratified by ethnicity showed a weak association between the IL-1βpolymorphism (rs16944) and chronic periodontitis in the Caucasian population (recessive model, OR = 1.34, 95% CI = 1.017–1.758,P=0.037).Conclusion. Evidences from a case-control study and the meta-analysis suggest that IL-1βpolymorphism (rs16944) is not associated with susceptibility to chronic periodontitis.


2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Yi Zhang ◽  
Tiecheng Pan ◽  
Xiaoxuan Zhong ◽  
Cai Cheng

Aim. To explore whether Chinese traditional medicine, tongxinluo (TXL), exerts beneficial effects on endothelial dysfunction induced by homocysteine thiolactone (HTL) and to investigate the potential mechanisms.Methods and Results. Incubation of cultured human umbilical vein endothelial cells with HTL (1 mM) for 24 hours significantly reduced cell viabilities assayed by MTT, and enhanced productions of reactive oxygen species. Pretreatment of cells with TXL (100, 200, and 400 μg/mL) for 1 hour reversed these effects induced by HTL. Further, coincubation with GW9662 (0.01, 0.1 mM) abolished the protective effects of TXL on HTL-treated cells. Inex vivoexperiments, exposure of isolated aortic rings from rats to HTL (1 mM) for 1 hour dramatically impaired acetylcholine-induced endothelium-dependent relaxation, reduced SOD activity, and increased malondialdehyde content in aortic tissues. Preincubation of aortic rings with TXL (100, 200, and 400 μg/mL) normalized the disorders induced by HTL. Importantly, all effects induced by TXL were reversed by GW9662.In vivoanalysis indicated that the administration of TXL (1.0 g/kg/d) remarkably suppressed oxidative stress and prevented endothelial dysfunction in rats fed with HTL (50 mg/kg/d) for 8 weeks.Conclusions. TXL improves endothelial functions in rats fed with HTL, which is related to PPARγ-dependent suppression of oxidative stress.


2009 ◽  
Vol 23 (6) ◽  
pp. 431-436 ◽  
Author(s):  
GY Minuk ◽  
R Greenberg ◽  
J Uhanova ◽  
K Hawkins ◽  
WD Leslie

BACKGROUND: Unconjugated bilirubin inhibits osteoblastic proliferative activity in vitro, raising the possibility that Gilbert’s syndrome (GS) patients are at increased risk of osteoporosis.OBJECTIVES: To compare bone mineral density (BMD), serum parathyroid hormone (PTH), C-telopeptide (CTX) and osteocalcin levels in GS subjects versus matched controls in a cross-sectional, case-control study.METHODS: BMD determinations were obtained with central dual-energy x-ray absorptiometry. Serum PTH, CTX and osteocalcin levels were measured by enzyme immunoassay.RESULTS: A total of 17 GS and 30 control subjects were studied. Overall, there were no significant differences in BMD, PTH, CTX or osteocalcin levels between the two groups. However, when older (older than 40 years of age) and younger (40 years of age and younger) cohorts were considered separately, the older GS cohort had significantly decreased total hip BMD, T scores and Z scores, and femoral neck BMD, T scores and Z scores (P<0.005 for each parameter, respectively) compared with older control subjects. Serum osteocalcin levels were lower in the older versus younger GS cohort (P=0.006). An inverse correlation existed between all subjects’ serum unconjugated bilirubin levels and total body BMD determinations (r=−0.42; P=0.04). On univariate analysis, the association between serum unconjugated bilirubin and total body BMD was not significant (P=0.066), nor was serum unconjugated bilirubin identified as a risk factor for low BMD when entered into multivariate analyses.CONCLUSIONS: The results of the present pilot study warrant further research involving larger numbers of subjects and longitudinal measurements to determine whether GS is associated with decreased BMD, particularly in older GS subjects.


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