Oxidative Stress In Systemic Lupus Erythematosus Research Articles

Exploring the XIST axis as oxidative stress-related signatures in systemic lupus erythematosus.

In the pathogenesis of systemic lupus erythematosus (SLE), oxidative stress (OS) plays an complex role; nevertheless, few investigations have indicated a ceRNA-based mechanism involved. The aim of this study was to explore the ceRNA regulation mechanism of oxidative stress in SLE and provide new therapeutic targets for SLE. Three datasets from the Gene Expression Omnibus (GEO) database were used to obtain differentially expressed lncRNAs, miRNAs, and mRNAs (DElncRNAs, DEmiRNAs, and DEmRNAs). Functional analysis was explored and a triple ceRNA network was built. Least absolute shrinkage and selection operator regression was used to find optimal signatures. The sensitivity and specificity of the signatures were examined and validated using receiver operating characteristic (ROC) analysis. The CIBERSORT algorithm was used to investigate immune infiltration features. Moreover, the hub mRNAs were validated by quantitative real-time PCR. 42 DEmRNAs were identified. Enrichment analysis showed that the DEmRNAs were primarily concentrated in neutrophil-associated biological processes. The ROC curve found FOS and MME provided potential biomarkers for identifying SLE patients. And the XIST/FOS and XIST/MME axes were identified the possible OS-related regulatory pathway in SLE. Immune infiltration showed that resting memory CD4 T cells presented a lower level. This study constructed the ceRNA-based XIST/FOS and XIST/MME axes as prospective OS-related signatures for SLE. Our findings provide new insights into the pathogenesis of SLE and shed a novel light on therapeutic strategies.

Oxidative Stress in SLE T Cells, Is NRF2 Really the Target to Treat?

Oxidative stress is a major component of cellular damage in T cells from patients with systemic lupus erythematosus (SLE) resulting amongst others in the generation of pathogenic Th17 cells. The NRF2/Keap1 pathway is the most important antioxidant system protecting cells from damage due to oxidative stress. Activation of NRF2 therefore seems to represent a putative therapeutic target in SLE, which is nevertheless challenged by several findings suggesting tissue and cell specific differences in the effect of NRF2 expression. This review focusses on the current understanding of oxidative stress in SLE T cells and its pathophysiologic and therapeutic implications.

Increased Mitochondrial Electron Transport Chain Activity at Complex I Is Regulated byN-Acetylcysteine in Lymphocytes of Patients with Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) patients' peripheral blood lymphocytes (PBL) show mitochondrial dysfunction and oxidative stress. To determine the electrochemical bases of mitochondrial dysfunction, we measured electron transport chain (ETC) activity and its regulation by N-acetylcysteine (NAC) that reversed glutathione depletion and improved disease activity in SLE. ETC activity was assessed in PBL of 69 SLE patients and 37 healthy donors. Negatively isolated T cells were examined in 7 SLE patients, 11 healthy donors, and 10 nonlupus inflammatory arthritis (IA) donors. O₂ consumption (in nmol/ml/min) by lupus PBL was increased at baseline (SLE: 2.492±0.196, control: 2.137±0.153; p=0.027) and with complex IV substrates (SLE: 7.722±0.419, control: 7.006±0.505; p=0.028). SLE PBL consumed more O₂ upon in-chamber T-cell activation (p=0.012). After overnight T-cell stimulation, ETC activity of SLE PBL was 2.27-fold increased through complex I (SLE: 1.606±0.273, control: 0.709±0.169; p=0.001) and, to a lesser extent, through complex IV. Likewise, complex I activity was elevated in negatively isolated "untouched" T cells of SLE patients (1.816±0.180) relative to healthy controls (0.917±0.094; p=0.0003) and IA disease controls studied in parallel (1.057±0.199; p=0.0308). NAC diminished O₂ consumption through complex I and H₂O₂ levels both in SLE and in control PBL. O₂ consumption was found to be increased in SLE patients' PBL relative to control subjects evaluated in parallel. ETC complex I is identified as the main source of oxidative stress in SLE. Lupus PBL exhibit increased O₂ consumption through mitochondrial ETC complex I that is inhibited by NAC, which may have therapeutic efficacy through reducing oxidative stress in SLE.

Oxidative stress and its biomarkers in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune inflammatory disease whose etiology remains largely unknown. The uncontrolled oxidative stress in SLE contributes to functional oxidative modifications of cellular protein, lipid and DNA and consequences of oxidative modification play a crucial role in immunomodulation and trigger autoimmunity. Measurements of oxidative modified protein, lipid and DNA in biological samples from SLE patients may assist in the elucidation of the pathophysiological mechanisms of the oxidative stress-related damage, the prediction of disease prognosis and the selection of adequate treatment in the early stage of disease. Application of these biomarkers in disease may indicate the early effectiveness of the therapy. This review is intended to provide an overview of various reactive oxygen species (ROS) formed during the state of disease and their biomarkers linking with disease. The first part of the review presents biochemistry and pathophysiology of ROS and antioxidant system in disease. The second part of the review discusses the recent development of oxidative stress biomarkers that relates pathogenesis in SLE patients and animal model. Finally, this review also describes the reported clinical trials of antioxidant in the disease that have evaluated the efficacy of antioxidant in the management of disease with ongoing conventional therapy.

Malondialdeído e grupo sulfidrila como biomarcadores do estresse oxidativo em pacientes com lúpus eritematoso sistêmico

Systemic lupus erythematosus (SLE) is an autoimmune disease of unknown origin associated with oxidative stress. The present study aimed to investigate the presence of oxidative stress in patients with newly diagnosed SLE. SLE patients (n = 36) and control subjects (n = 28) were enrolled in this study. Blood samples were used for malondialdehyde (MDA), sulfhydryl groups (SH) and uric acid determination. MDA levels (µmol/L) were higher in patients (3.9 ± 2.6) than in control subjects (1.6 ± 2.6). SH were significantly lower in SLE patients. The findings suggest that MDA can be a good marker of oxidative stress in SLE.

Association of catalase gene polymorphisms with catalase activity and susceptibility to systemic lupus erythematosus in the Suez Canal area, Egypt

The present study evaluated the relationship of genetic variants in both promoter (-262 C/T) and in exonic (389 C/T) regions of the catalase (CAT) gene to CAT activity and risk of systemic lupus erythematosus (SLE) in Suez Canal-area patients. CAT gene polymorphisms were assessed by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). CAT activity was measured by using a spectrophotometer. We compared the frequencies of CAT 389 C/T and -262 C/T polymorphic variants between SLE patients (n = 103) and healthy controls (n = 103). CAT 389 C/T is associated with SLE susceptibility, with the T allele being significantly more frequent among SLE patients than healthy controls. There was no association, however, between CAT activity and genotypes of 389 C/T. We did not observe significant differences in the prevalence of CAT -262 C/T polymorphic variants in SLE patients and controls, however, we found that patients with the CAT -262 CT and TT genotypes had low CAT activity, and these genotypes showed a significant association with thrombocytopaenia, leukopaenia and the presence of anti-snRNP in SLE patients. In conclusion, the present study supports the notion of invivo oxidative stress in SLE as indicated by the decrease in CAT activity. The allelic variations in the CAT gene -262 are more likely to affect the expression or the function of the enzyme. Since CAT may be pathogenetically linked to SLE, and owing to its free-radical origin, it appears reasonable to target lipid peroxidation by dietary and/or pharmacological antioxidants.