scholarly journals The role of oxidative stress in the pathogenesis of Graves’ orbitopathy

2021 ◽  
Vol 75 ◽  
pp. 448-455
Author(s):  
Magdalena Londzin-Olesik ◽  
Beata Kos-Kudła ◽  
Aleksandra Nowak ◽  
Mariusz Nowak
Keyword(s):  
Oxidative Stress ◽  
T Cell Activation ◽  
Cell Activation ◽  
Serum Levels ◽  
Thyroid Stimulating Hormone ◽  
Peroxidation Of Lipids ◽  
Hormone Production ◽  
Stress Markers ◽  
Orbital Tissue ◽  
Autoimmune Condition

Graves’ disease (GD) is a chronic autoimmune condition in which the anti-thyroid stimulating hormone receptor antibodies (TRAb) activate the thyrotropin receptor (TSHR) located on thyrocytes, leading to excessive thyroid hormone production. TSHR is also expressed in extrathyroidal tissues, in particular, within the orbit. The serum levels of TRAb correlate with the severity and activity of thyroid orbitopathy (TO). TO is the most common extrathyroidal manifestation of GD. It is an autoimmune inflammation of orbital tissues, that is, extraocular muscles, orbital adipose tissue or a lacrimal gland. Increased orbital fibroblast and adipocyte proliferation, overproduction of glycosaminoglycans, as well as extraocular muscle oedema, result in increased orbital tissue volume and trigger the onset of TO symptoms. The pathophysiology of TO is complex and has not been fully unexplained to date. Orbital fibroblasts show expression of the TSHR, which is the main target of autoimmunity. It has been hypothesised that T-cell activation induced by orbital receptor stimulation by the target antibody results in orbital tissue infiltration, triggering a cascade of events which leads to the production of cytokines, growth factors and reactive oxygen species (ROS). ROS cause damage to many components of the cell: the cell membrane through the peroxidation of lipids and proteins leading to a loss of their function and enzymatic activity. Oxidative stress leads to the activation of the antioxidant system, which operates through two mechanisms: enzymatic and non-enzymatic. Assessment of the concentration of oxidative stress markers and the concentration or activity of anti-oxidative system parameters enables the evaluation of oxidative stress severity, which in the future may be utilized to assess treatment efficacy and prognosis in patients with active OT.

The role of oxidative stress in the pathogenesis of Graves’ orbitopathy

2021 ◽  
Vol 75 ◽  
pp. 1-10
Author(s):  
Magdalena Londzin-Olesik ◽  
Beata Kos-Kudła ◽  
Aleksandra Nowak ◽  
Mariusz Nowak
Keyword(s):  
Oxidative Stress ◽  
T Cell Activation ◽  
Cell Activation ◽  
Serum Levels ◽  
Thyroid Stimulating Hormone ◽  
Peroxidation Of Lipids ◽  
Hormone Production ◽  
Stress Markers ◽  
Orbital Tissue ◽  
Autoimmune Condition

Graves' disease (GD) is a chronic autoimmune condition, in which the anti-thyroid stimulating hormone receptor antibodies (TRAb) activate the thyrotropin receptor (TSHR) located on thyrocytes, leading to excessive thyroid hormone production. TSHR is also expressed in extrathyroidal tissues, in particular, within the orbit. The serum levels of TRAb corelate with severity and activity of thyroid orbitopathy (TO). TO is the most common extrathyroidal manifestation of GD. It is an autoimmune inflammation of orbital tissues, that is, extraocular muscles, orbital adipose tissue or a lacrimal gland. Increased orbital fibroblast and adipocyte proliferation, overproduction of glycosaminoglycans, as well as extraocular muscle oedema result in an increased orbital tissue volume and trigger the onset of TO symptoms. The pathophysiology of TO is complex and has not been fully unexplained to date. Orbital fibroblasts show expression of the TSHR, which is the main target of autoimmunity. It has been hypothesised that T-cell activation induced by orbital receptor stimulation by the target antibody results in orbital tissue infiltration, triggering a cascade of events which leads to the production of cytokines, growth factors and reactive oxygen species (ROS). ROS cause damage to many components of the cell: the cell membrane through the peroxidation of lipids and proteins leading to a loss of their function and enzymatic activity. Oxidative stress leads to activation of the antioxidant system which operates through two mechanisms: enzymatic and non-enzymatic. Assessment of the concentration of oxidative stress markers and the concentration or activity of antioxidative system parameters enables evaluation of oxidative stress severity, which in the future may be utilized for assessment of treatment efficacy and prognosis in patients with active OT.

Oxidative Stress Markers and Metal Ions are Correlated With Cognitive Function in Alzheimer’s Disease

2017 ◽  
Vol 32 (6) ◽  
pp. 353-359 ◽  
Author(s):  
Zhengping Pu ◽  
Wenjie Xu ◽  
Yong Lin ◽  
Jincai He ◽  
Manli Huang
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Metal Ions ◽  
Serum Levels ◽  
Zinc Level ◽  
Copper Level ◽  
Iron Level ◽  
Oxidative Stress Markers ◽  
Stress Markers

We investigated oxidative stress markers and metal ions in patients with Alzheimer’s disease (AD). The serum levels of ceruloplasmin (CER), C-reactive protein (CRP), uric acid (UA), homocysteine (Hcy), copper, iron, and zinc were determined in 125 patients with AD (mild, n = 2 8; moderate, n = 42; and severe, n = 55) and 40 healthy control (HC) participants. Compared to HC, CER and UA levels were significantly lower in moderate and severe AD groups, whereas CRP and Hcy levels were significantly higher in the severe AD group. Copper level was significantly higher in moderate and severe AD groups than the other groups. Compared to HC, iron level was significantly higher in patients with AD, whereas zinc level was significantly lower in patients with AD. In patients with AD, the severity of cognitive impairment was positively correlated with CER, UA, and zinc levels, whereas it was negatively correlated with copper level. Taken together, our findings provide a novel approach to assess AD progression.

scholarly journals Role of Oxidative Stress and the Identification of Biomarkers Associated With Thyroid Dysfunction in Schizophrenics

2021 ◽  
Vol 12 ◽  
Author(s):  
Mahmood Rasool ◽  
Arif Malik ◽  
Shamaila Saleem ◽  
Muhammad Abdul Basit Ashraf ◽  
Altaf Qadir Khan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Function ◽  
Vitamin B6 ◽  
Thyroid Dysfunction ◽  
Total Bilirubin ◽  
Thyroid Stimulating Hormone ◽  
Dietary Antioxidants ◽  
Iodide Uptake ◽  
Control Subjects ◽  
Stress Markers

Background: Schizophrenia is associated with a deficiency of dietary antioxidants like vitamin B6, B9, and B12 resulting in defective methylation leading to hyperhomocysteinemia. Hyperhomocysteinemia causes mitochondrial DNA damage, oxidative stress, vascular damage, and lipid peroxidation. Oxidative stress and increase in reactive oxygen species result in 8-oxodG production which induces apoptosis of both astrocytes and thyrocytes thus predisposing them to thyroid dysfunction and neurodegeneration. Furthermore, the presence of excessive free radicals increases thyroid thermogenesis causing hyperthyroidism or its excess may cause hypothyroidism by inhibiting iodide uptake. In the present study, we evaluated the various biomarkers associated with thyroid dysfunction in schizophrenics.Materials and Methods: 288 patients suffering from schizophrenia and 100 control subjects were screened for liver function tests (LFTs) such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin (TB). Also, the stress markers, namely malondialdehyde (MDA), homocysteine, cysteine, methionine, the thyroid profile including triiodothyronine (T3), thyroxine (T4), thyroid-stimulating hormone (TSH), thyroxine peroxide antibody (TPO-Ab); TSH receptor-Ab (TSHr-Ab), dietary antioxidants, lipids, cytokines, aminoacids and hormones, vitamins and trace elements, and other biochemical parameters.Results: The LFTs showed elevated levels of ALT (45.57 ± 4.87 Vs. 26.41 ± 3.76 U/L), AST (40.55 ± 1.34 Vs. 21.92 ± 3.65 U/L), ALP (121.54 ± 4.87 Vs. 83.76 ± 5.87 U/L), and total bilirubin (2.63 ± 0.987 Vs. 1.10 ± 0.056 mg/dl), in schizophrenics than controls. Increased levels of MDA (3.71 ± 0.967 Vs. 1.68 ± 0.099) and homocysteine (17.56 ± 2.612 Vs. 6.96 ± 1.987 μmol/L were observed in schizophrenics compared to the controls, indicating increased stress. Levels of cysteine and methionine were decreased in schizophrenics than the controls (1.08 ± 0.089 Vs. 4.87 ± .924 μmol/L and 17.87 ± 1.23 Vs. 99.20 ± 5.36 μmol/L). The levels of TPO-Ab (IU/ml), Tg-Ab (pmol/L), and TSHr-Ab (IU/L) were observed to be higher in the patients’ group as compared to control subjects (9.84 ± 2.56 Vs. 5.81 ± 1.98, 55.50 ± 2.98 Vs. 32.95 ± 2.87 and 2.95 ± 0.0045 Vs. 1.44 ± 0.0023 respectively). Levels of Vitamin B6, B9, and B12 were also significantly decreased in the patients compared to the healthy controls.Conclusion: The schizophrenics, demonstrated altered liver function, increased stress markers, and decreased dietary antioxidants. Reduced primary and secondary antioxidant levels, may result in hyperhomocysteinemia and cause further DNA and mitochondrial damage. Therefore, homocysteine and/or prolactin levels may serve as candidate prognostic markers for schizophrenia. Also, both neurological symptoms and the susceptibility to thyroid disorders may be prevented in the initial stages of this debilitating disorder by appropriate dietary supplementation of antioxidants which can rectify a reduction in primary and secondary antioxidants, and disturbed prolactin-serotonin-dopamine interactions in schizophrenics.

scholarly journals SLFN2 protection of tRNAs from stress-induced cleavage is essential for T cell–mediated immunity

Science ◽  
2021 ◽  
Vol 372 (6543) ◽  
pp. eaba4220 ◽  
Author(s):  
Tao Yue ◽  
Xiaoming Zhan ◽  
Duanwu Zhang ◽  
Ruchi Jain ◽  
Kuan-wen Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Interleukin 2 ◽  
Cell Receptor ◽  
Cell Mediated Immunity ◽  
Activated T Cells ◽  
Granule Formation

Reactive oxygen species (ROS) increase in activated T cells because of metabolic activity induced to support T cell proliferation and differentiation. We show that these ROS trigger an oxidative stress response that leads to translation repression. This response is countered by Schlafen 2 (SLFN2), which directly binds transfer RNAs (tRNAs) to protect them from cleavage by the ribonuclease angiogenin. T cell–specific SLFN2 deficiency results in the accumulation of tRNA fragments, which inhibit translation and promote stress-granule formation. Interleukin-2 receptor β (IL-2Rβ) and IL-2Rγ fail to be translationally up-regulated after T cell receptor stimulation, rendering SLFN2-deficient T cells insensitive to interleukin-2’s mitogenic effects. SLFN2 confers resistance against the ROS-mediated translation-inhibitory effects of oxidative stress normally induced by T cell activation, permitting the robust protein synthesis necessary for T cell expansion and immunity.

scholarly journals Blockade of Costimulation Prevents Infection-Induced Immunopathology in Interleukin-10-Deficient Mice

2000 ◽  
Vol 68 (5) ◽  
pp. 2837-2844 ◽  
Author(s):  
Eric N. Villegas ◽  
Ulrike Wille ◽  
Linden Craig ◽  
Peter S. Linsley ◽  
Donna M. Rennick ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Serum Levels ◽  
Cd40 Ligand ◽  
Interleukin 10 ◽  
Cell Mediated Immunity ◽  
Ifn Γ ◽  
Oxide Synthase

ABSTRACT Interleukin-10 (IL-10) is associated with inhibition of cell-mediated immunity and downregulation of the expression of costimulatory molecules required for T-cell activation. When IL-10-deficient (IL-10KO) mice are infected with Toxoplasma gondii, they succumb to a T-cell-mediated shock-like reaction characterized by the overproduction of IL-12 and gamma interferon (IFN-γ) associated with widespread necrosis of the liver. Since costimulation is critical for T-cell activation, we investigated the role of the CD28-B7 and CD40-CD40 ligand (CD40L) interactions in this infection-induced immunopathology. Our studies show that infection of mice with T. gondii resulted in increased expression of B7 and CD40 that was similar in wild-type and IL-10KO mice. In vivo blockade of the CD28-B7 or CD40-CD40L interactions following infection of IL-10KO mice with T. gondii did not affect serum levels of IFN-γ or IL-12, nor did it prevent death in these mice. However, when both pathways were blocked, the IL-10KO mice survived the acute phase of infection and had reduced serum levels of IFN-γ and alanine transaminase as well as decreased expression of inducible nitric oxide synthase in the liver and spleen. Analysis of parasite-specific recall responses from infected IL-10KO mice revealed that blockade of the CD40-CD40L interaction had minimal effects on cytokine production, whereas blockade of the CD28-B7 interaction resulted in decreased production of IFN-γ but not IL-12. Further reduction of IFN-γ production was observed when both costimulatory pathways were blocked. Together, these results demonstrate that the CD28-B7 and CD40-CD40L interactions are involved in the development of infection-induced immunopathology in the absence of IL-10.

scholarly journals Association of CD28 IVS3 +17T/C Polymorphism with Soluble CD28 in Rheumatoid Arthritis

2011 ◽  
Vol 30 (1) ◽  
pp. 25-29 ◽  
Author(s):  
I. Y. Ledezma-Lozano ◽  
J. J. Padilla-Martínez ◽  
S. D. Leyva-Torres ◽  
I. Parra-Rojas ◽  
M. G. Ramírez-Dueñas ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cell ◽  
T Cell Activation ◽  
Healthy Subjects ◽  
Cell Activation ◽  
Costimulatory Molecule ◽  
Serum Levels ◽  
Unknown Etiology ◽  
Clinical Activity ◽  
Western Mexico

Objective:Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology in which inflammatory pathology involves T cell activation and the CD28 costimulatory molecule involved in T cell presentation. The gene includes the CD28 IVS3 +17T/C polymorphism that could be associated with susceptibility to RA whereas the soluble concentrations of CD28 (sCD28) could be related to clinical activity.Methods:We investigated the CD28 IVS3 +17T/C polymorphism in 200 RA patients and 200 healthy subjects (HS). Furthermore, we quantified the sCD28 concentrations in 77 samples of each group. We applied indexes focused to determine the activity and disability (DAS28 and Spanish HAQ-DI, respectively) in RA patients.Methods:We investigated the CD28 IVS3 +17T/C polymorphism in 200 RA patients and 200 healthy subjects (HS). Furthermore, we quantified the sCD28 concentrations in 77 samples of each group. We applied indexes focused to determine the activity and disability (DAS28 and Spanish HAQ-DI, respectively) in RA patients.Results:RA patients had significantly higher frequencies of the CD28 T allele compared to HS (p= 0.032 OR = 1.59, C.I. 1.02–2.49). In addition, the IVS3 +17 T/T genotype frequency was also increased in RA vs. HS (p= 0.026). The RA patients showed higher sCD28 serum levels than HS (p= 0.001). Carriers of the T/T genotype in RA patients showed higher sCD28 levels than C/C carriers (p= 0.047). In addition, a correlation between sCD28 and Spanish HAQ-DI (correlation, 0.272;p= 0.016), was found.Conclusion:The T allele in CD28 IVS3 +17T/C polymorphism is associated with a susceptibility to RA in Western Mexico. In addition, increased sCD28 levels are related to T/T genotype in RA patients.

Areca nut extract suppresses T-cell activation and interferon-γ production via the induction of oxidative stress

2007 ◽  
Vol 45 (8) ◽  
pp. 1410-1418 ◽  
Author(s):  
C.C. Wang ◽  
T.Y. Liu ◽  
S.P. Wey ◽  
F.I. Wang ◽  
T.R. Jan
Keyword(s):  
Oxidative Stress ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Interferon Γ ◽  
Areca Nut

scholarly journals Serum Levels of Oxidative Stress Markers in Patients with Type 2 Diabetes Mellitus and Non-alcoholic Steatohepatitis

2016 ◽  
Vol 54 (4) ◽  
pp. 228-236 ◽  
Author(s):  
F. Casoinic ◽  
D. Sampelean ◽  
Anca D. Buzoianu ◽  
N. Hancu ◽  
Dorina Baston
Keyword(s):  
Oxidative Stress ◽  
Fatty Liver Disease ◽  
Serum Levels ◽  
Protein Carbonyls ◽  
Oxidative Stress Markers ◽  
Multivariate Logistic Regression ◽  
Alcoholic Fatty Liver ◽  
Stress Markers ◽  
Alcoholic Fatty Liver Disease

Abstract Introduction. Oxidative stress is one of the key mechanisms responsible for disease progression in non-alcoholic fatty liver disease. The aim of this study was to evaluate the serum levels of oxidative stress markers in patients with type 2 diabetes mellitus (DMT2) and non-alcoholic steatohepatitis (NASH) and test their relationships with clinical and biochemical patient characteristics, compared to patients with DMT2 without non-alcoholic fatty liver disease (NAFLD), and controls. Materials and methods. In all, 60 consecutive patients with DMT2 and NASH, 55 with DMT2 without NAFLD, and 50 age-and-gender-matched healthy subjects participated in the study. The serum levels of protein carbonyls and 8-isoprostane were determined by ELISA methods, while the serum levels of malondialdehyde (MDA) were detected by means of the spectrophotometric method. Clinical, demographic, and laboratory parameters were examined for all the subjects included in the study. Multivariate logistic regression was used to test the independent predictive factors in the relationships investigated here. Results. Patients with DMT2 and NASH displayed significantly higher serum levels of protein carbonyls (1.112 ± 0.42 nmol/dL), MDA (6.181 ± 1.81 ng/mL), and 8-isoprostane (338.6 ± 98.5 pg/mL) compared to patients with DMT2 without NAFLD, and controls. Results of multivariate logistic regression analyses indicate that in patients with DMT2 and NASH, the serum levels of oxidative stress markers were independently and positively associated with: HbA1c, duration of diabetes, the UKPDS cardiovascular risk score (for protein carbonyls); age, LDL-cholesterol (for 8-isoprostane); and triglycerides serum levels (for MDA). Conclusions. Our findings indicate that the process of oxidative stress tends to increase in patients with DMT2 and NASH, compared to patients with DMT2 without NAFLD, and controls. This evidence suggests that an antioxidant therapy might prove useful in the treatment of patients with DMT2 and NASH.

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