Figure 1 - available from: Autoimmunity Highlights
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Schematic representation of the three major reactive oxygen species (superoxide, hydrogen peroxide, and hydroxyradical) and the enzymatic pathways that produce them. NADH nicotinamide adenine dinucleotide, NADPH nicotinamide adenine dinucleotide phosphate, GSH glutathione, GSSG glutathione disulfide, SOD superoxide dismutase, NOS nitric oxide synthases, MAO monoamine oxidase, MPO myeloperoxidase
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Reactive oxygen species (ROS) have been extensively studied in the induction of inflammation and tissue damage, especially as it relates to aging. In more recent years, ROS have been implicated in the pathogenesis of autoimmune diseases. Here, ROS accumulation leads to apoptosis and autoantigen structural changes that result in novel specificities....
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Background
Hashimoto thyroiditis (HT) is an autoimmune disease which may result in extensive damage of the thyroid gland. Chronic atrophic gastritis (CAG), is the most frequent HT-associated disorder, with anti-parietal cell autoantibodies (APCA) being a screening test for autoimmune CAG. The aim of this study was to investigate, in a cohort of HT...
Citations
... Oxidative stress damage is pivotal in the etiology of vitiligo, being considered as one of the most crucial initiators of this condition (Di Dalmazi et al., 2016;Chen et al., 2021). The secretion of growth factors, release of pro-inflammatory cytokines, and activation of inflammasomes within keratinocytes can exacerbate oxidative stress and promote immune responses, thus inducing or exacerbating the development of vitiligo . ...
Introduction: Vernonia anthelmintica (L.) Willd. is a traditional treatment for vitiligo in Xinjiang. However, its therapeutic mechanism remains unclear owing to its complex composition and limited research on its chemical profile.
Methods: We employed a targeted metabolome approach, combining selective reaction monitoring/multiple response monitoring (SRM/MRM) with high-performance liquid chromatography and MRM mass spectrometry to quantitatively analyze the flavonoid constituents of Vernonia anthelmintica . We also used network pharmacology and molecular docking to identify potential vitiligo-linked compounds and targets of V. anthelmintica seeds. Additionally, we assessed HaCaT cell proliferation by AAPH-induced , alongside changes in SOD activity and MDA content, following treatment with V. anthelmintica components. Finally, flow cytometry was used to detect apoptosis and ROS levels.
Results and Discussion: We identified 36 flavonoid compounds in V. anthelmintica seeds, with 14 compounds exhibiting druggability. AKT1 , VEGFA , ESR1 , PTGS2 , and IL2 have been identified as key therapeutic target genes, with PI3K/AKT signaling being an important pathway. Notably, kaempferol, one of the identified compounds, exhibited high expression in network pharmacology analysis. Kaempferol exhibited a strong binding affinity to important targets. Further, kaempferol enhanced HaCaT cell viability, inhibited apoptosis, reduced MDA levels, suppressed ROS activity, and upregulated SOD activity, increase the expression of cellular antioxidant genes, including HO-1, GCLC, GCLM, Nrf2, NQO1 and Keap1, providing significant protection against oxidative stress damage in vitro . Here, we present the first comprehensive study integrating SRM/MRM approaches and network analysis to identify active flavonoid compounds within V. anthelmintica (L.) Willd. Moreover, we revealed that its active ingredient, kaempferol, offers protection against AAPH-induced damage in keratinocytes, highlighting its potential as a clinical resource.
... [16] Inflammatory reactions induced by the immune system, oxidative stress, and apoptotic processes play a significant role in thyroid follicular damage. [17,18] Hypothyroidism has also been linked with an increased level of insulin resistance (IR) and a higher incidence of atherosclerotic cardiovascular diseases. [19,20] In this study, we investigated fetuin-A, Nrf2, and CK18 levels in patients with Hashimoto's disease. ...
Objectives
Fetuin-A is a protein that exhibits proatherogenic, pro-inflammatory, and anti-inflammatory effects with increased insulin resistance and adipocyte dysfunction. The nuclear factor erythroid 2-related factor (Nrf2) is a transcription factor that is crucial for protecting cells against oxidative damage. As a cell death product, cytokeratin 18 (CK18) levels increase during necrosis and apoptosis of both normal and tumor cells. We analyzed the plasma levels of three biomarkers based on the hypothesis that they might be related to some pathophysiological pathways in Hashimoto’s disease.
Methods
We compared 34 female patients with overt hypothyroidism due to Hashimoto’s disease (Group 1) with 34 age-matched healthy females (Group 2). For comparison, plasma levels of thyroid-stimulating hormone (TSH), fetuin-A, Nrf2, and CK18 were measured in all participants.
Results
In group 1, the mean TSH levels (31.4±15.3) were significantly higher than those in group 2 (2.6±1.0) (p<0.001). The levels of mean fetuin-A (606.7±34.2) and Nrf2 (1.3±0.6) were found to be significantly higher in group 1 than in group 2 (440.0±34.2 vs. 0.7±0.2) (p<0.001 for both). CK18 levels in group 1 (0.36±0.13) were also significantly higher than in group 2 (0.26±0.16) (p=0.020). A significant correlation was observed between TSH levels and fetuin-A (r=0.401, p=0.001).
Conclusion
Increased levels of fetuin-A, Nrf2, and CK18 may be a consequence or cause of the pathophysiological pathways of Hashimoto’s disease. The clinical significance of increased levels of these biomarkers requires further investigation.
... Increasing the levels of ROS can also harm immunoglobulins and alter the DNA repair mechanisms. Di Dalmazi et al. 15 have shown that ROS oxidative stress plays an important role in the progression of RA. DPPH and H 2 O 2 assays were used to test the potential antioxidant activity of crude extracts from Saraca asoca, Ficus benghalensis, Chenopodium album, and Nyctanthes arbor-tristis. ...
Rheumatoid arthritis, a chronic autoimmune disorder, is characterized by polyarthralgia and joint dysfunction resulting from autoimmune responses that target self-neoepitopes. These attacks lead to the activation of macrophages and other defense cells. By identifying these self-epitopes as biomarkers in RA, researchers have gained valuable insights into the disease’s pathogenesis. Over the years, research has focused on investigating the potential of medicinal plants as antiinflammatory agents. In this study, a hydroethanolic extract of Saraca asoca, Ficus benghalensis, Chenopodium album, and Nyctanthes arbor-tristis leaves was prepared by Soxhlet apparatus. Various concentrations of extracts were utilized to assess phytochemical analysis, GC-MS, in-vitro anti-oxidant, and anti-inflammatory activities. The highest scavenging potential was exhibited by Chenopodium album, as assessed by the DPPH assay (90.32 ± 3.2 %) and H2O2 (86.00 ± 1.94 %). Similarly, the Nyctanthes arbor-tristis showed (92.23 ± 0.83 %) inhibition in membrane stabilization assay, and (91.49 ± 1.03 %) in protein denaturation inhibition capacity. GCMS analysis showed various phytoconstituents in extracts. In order to confirm its therapeutic potential for treating RA, Nyctanthes arbor-tristis may be a better drug candidate that needs to be further researched for mechanistic studies.
... Excess free radical production results in various disorders including the vascular system such as atherosclerosis, vascular cell damage hypertension, restenosis, vasculitis, and abdominal aortic aneurysm Cheng et al. 2022). It is well established that body naturally produces antioxidants to counteract free radicals, but imbalance results in oxidative stress leading to excess reactive oxygen species (ROS) production that consequently leads to immune pathologies as evidenced by inflammation and tissue damage (Chaudhary et al. 2023;Di Dalmazi et al. 2016). In the vascular system, excessive production of ROS results in disruption of endothelial barrier integrity, which subsequently leads to tissue injury, increase in vascular permeability, and compromised organ functions (He, Talukder, and Gao 2020). ...
Ammi visnaga (A. visnaga) is an annual herb that has been used in traditional medicine to treat various ailments attributed to the presence of its bioactive compounds. The purpose of this study was to identify and examine the phytochemical properties of the hydroalcoholic extract of A. visnaga using in vitro and in vivo models. Our findings demonstrated that the extract contained a variety of beneficial components, including phenols, flavonoids, tannins, coumarins, saponins, khellin, and visnagin. The total polyphenolic content and total flavonoid content were 23.26 mg/GAE/g dry weight and 13.26 mg/GAE/g dry weight, respectively. In vitro tests demonstrated that the extract possessed antioxidant properties as evidenced by the ability to scavenge free radicals, including DPPH, ABTS, nitric oxide (NO), phosphomo-lybdate, and ferric-reducing antioxidant power (FRAP). Further, the extract was found to inhibit hydrogen peroxide (H 2 O 2)-induced hemolysis. In a 90-d in vivo study, female Wistar rats were administered 1 g/kg of A. visnaga extract orally resulting in a significant increase in total white blood cell count. Although morphological changes were observed in the liver, no marked alterations were noted in kidneys and spleen. In a female Swiss albino mice model of acetic acid-induced vascular permeability, A. visnaga significantly inhibited extravasations of Evans blue at doses of 0.5 or 1 g/kg with inhibition percentages of 51 and 65%, respectively, blocking tissue necrosis. The extract also demonstrated potential immunomodulatory properties in mice by enhancing antibody production in response to antigens. In silico molecular docking studies demonstrated a strong affinity between khellin or visnagin and immunomo-dulatory proteins, NF-κB, p52, and TNF-α. These findings suggest that A. visnaga may be considered a beneficial antioxidant with immunomodulatory properties and might serve as a therapeutic agent to combat certain diseases.
... Відомо, що вільні радикали відіграють важливу роль у нормальному і патологічному метаболізмі всіх клітинних форм життя, адже є невід'ємною частиною багатьох хімічних і біологічних процесів в організмі [1]. Найважливішим типом радикалів, що утворюються в живих системах, є активні форми кисню (АФК), зокрема такі, як супероксидний радикал, пероксид водню та гідроксильний радикал [2]. Доведено, що невелика кількість цих активних форм кисню необхідна для нормального перебігу багатьох фізіологічних процесів, зокрема передачі сигналів, синтезу клітинних структур, регуляції проникності мембран тощо [3]. ...
Мета роботи. Дослідження впливу водно-етанольного (30:70) екстракту з «волохатих» коренів Artemisia tilesii на процес утворення супероксидних радикалів у redоx системі автоокиснення адреналіну. Матеріали і методи. Водно-етанольний (30:70) екстракт з «волохатих» коренів Artemisia tilesii був отриманий у лабораторії адаптаційної біотехнології Інституту клітинної біології та генетичної інженерії НАН України. Загальний вміст флавоноїдів у екстракті з «волохатих» коренів Artemisia tilesii визначали спектрофотометричним методом та виражали у рутиновому еквіваленті. Дослідження впливу екстракту з «волохатих» коренів Artemisia tilesii на супероксидні радикали, які генеруються при автоокисненні адреналіну, проводили in vitro спектрофотометрично. Кількісну оцінку процесу здійснювали через розрахунок констант швидкості першого порядку. Результати й обговорення. Встановлено, що водно-етанольний (30:70) екстракт з «волохатих» коренів Artemisia tilesii, багатий на сполуки флавоноїдної природи, в хімічній системі автоокиснення адреналіну достовірно виявляє прооксидантні властивості, які залежать від його концентрації в системі. Вже при концентрації екстракту в системі 50 мкМ (за рутином) константа швидкості хімічної реакції утворення супероксидних радикалів збільшується в 2,3 раза. Висновки. Результати підтверджують, що екстракт з «волохатих» коренів Artemisia tilesii у хімічній системі автоокиснення адреналіну виявляє прооксидантний ефект, стимулюючи утворення супероксидних радикалів. Зважаючи на дані досліджень, які вказують на те, що генерація активних форм кисню та їхній підвищений рівень безпосередньо пов’язані з антибактеріальною активністю, можна зробити припущення, що потенційно даний екстракт за рахунок прооксидантних властивостей може виявляти протимікробний ефект та використовуватися як активний фармацевтичний інгредієнт лікарських засобів з антибактеріальною дією.
... In HT patients, primary hypothyroidism occurs after the destruction of CD8 + and MF directly or with the help of released cytokines by NK-cells in ADCC (antibody-dependent cell-mediated cytotoxicity) of a sufficient number of follicular cells that produce TG (19, 20, 28). Accumulation of reactive oxygen species (ROS) in thyroid tissues leads to apoptosis of thyroid cells during HT (29). In HT patients, the induction of neutrophil extracellular traps (NET) increases, which depends on the accumulation of ROS through the activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and the production of interleukin (IL) IL-6 (30). ...
Thyroid hormones and essential elements iodine (I), selenium (Se), iron (Fe), copper (Cu), zinc (Zn), calcium (Ca), magnesium (Mg), etc. play an important role in the work of many organs and systems of the body, including the immune system and the thyroid gland, and a violation of their supply can be the cause of pathological changes in them. In pathology, the interaction between thyroid hormones (TG), minerals and the immune system is disturbed. The review of the literature examines the immunomodulatory role of TG, minerals, their properties, and their participation in the pathogenesis of autoimmune thyroid diseases (AITD). The study of the relationship between the excess or deficiency of minerals and AITD is described. The basis of the development of AITD - Hashimoto’s thyroiditis (HT), Graves’ disease (GD), Graves’ ophthalmopathy (GO) is the loss of immune tolerance to thyroid antigens - thyroid peroxidase (TPO), thyroglobulin (Tg) and thyroid-stimulating hormone receptor (TSH-R). Immune-mediated mechanisms - production of autoantibodies to thyroid antigens and lymphocytic thyroid infiltration - are involved in the pathogenesis of AITD. Insufficiency of regulatory T cells (Treg) and regulatory B cells (Breg), imbalance between Th17-lymphocytes and Treg-lymphocytes, abnormal production of pro-inflammatory cytokines has a significant influence on the progression of AITD. With AITD, the balance between oxidants and antioxidants is disturbed and oxidative stress (OS) occurs. The lack of modern effective pharmacological therapy of AITD prompted us to consider the mechanisms of influence, possibilities of immunocorrection of pathogenetic factors using TG, micro/macronutrients. In order to develop a more effective treatment strategy, as well as approaches to prevention, a critical analysis of the ways of immunotherapeutic use of dietary supplements of I, Se, Zn, Mg and other minerals in AITD was carried out.
... The existence of the process of oxidative stress and autoimmunity, especially with the presence of genetic susceptibility, affects the occurrence of vitiligo. Elevated lipid peroxidase levels are a marker of oxidative stress in the early stages of vitiligo, indicating that ROS may be considered as an important early factor in inducing vitiligo and facilitating melanocyte loss.14,19,20 Melanocytes are the main target exposed to ROSduring the process of melanogenesis. ...
Vitiligo is a depigmentation disorder that is commonly found in the community. The causes of vitiligo are multifactorial such as genetic and environmental factors accompanied by the presence of non-specific and specific immune system factors. Melanocytes are the main target exposed by reactive oxygen species (ROS) during the process of melanogenesis. Such exposure can cause loss of homeostasis and cell death and has implications for vitiligo. Clinical manifestations of vitiligo are generally white depigmented macular lesions that are well demarcated. Based on its distribution, vitiligo can be divided into segmental and non-segmental vitiligo different in terms of prognosis, treatment and resolution of vitiligo.
... OS has been involved in the pathogenesis of several inflammatory and immunemediated disorders [1][2][3]7], such as cardiovascular diseases, diabetes, neurodegenerative diseases, cancer [7], and autoimmune diseases (AIDs), including thyroid AID [3,[13][14][15]. In autoimmune thyroid disorders (AITD), excess ROS could induce the modification of tissue proteins, which become neo-antigens or may dysregulate the immune system, promoting the onset of an AITD in genetically predisposed individuals [16,17]. ...
... In autoimmune thyroid disorders (AITD), excess ROS could induce the modification of tissue proteins, which become neo-antigens or may dysregulate the immune system, promoting the onset of an AITD in genetically predisposed individuals [16,17]. Moreover, excess ROS increases the proinflammatory state by enhancing the synthesis and release of cytokines, further contributing to tissue damage and disease progression [3,13]. ...
(1) Background: This paper aims to assess the existence of significant differences between two dietary regimes (omnivorous vs. semi-vegetarian) with reference to some oxidative stress markers (SOD, GPx, TRxR, GR, AGEs, and AOPPs) using non-parametric combination methodology based on a permutation test. (2) Methods: At the endocrinology unit of Messina University Hospital, two hundred subjects were asked to fill out a questionnaire about their dietary habits. None were under any pharmacological treatment. Using the NPC test, all comparisons were performed stratifying patients according to gender, age (≤40 or >40 years), BMI (normal weight vs. overweight), physical activity (sedentary vs. active lifestyle), TSH, FT4 levels in quartiles, and diagnosis of Hashimoto’s thyroiditis. We evaluated differences in oxidative stress parameters in relation to two examined dietary regimes (omnivorous vs. semi-vegetarian). (3) Results: The antioxidant parameters GPx and TRxR were significantly lower in subjects with an omnivorous diet than in semi-vegetarians, particularly in females, both age groups, subjects with normal weight, those not affected by Hashimoto’s thyroiditis, and both the sedentary and active lifestyle groups. Finally, the AGE and AOPP markers were significantly lower in semi-vegetarians. (4) Conclusion: Thanks to the NPC methodology, we can state that dietary patterns exert a significant influence on some oxidative stress parameters.
... There is evidence that air pollution including PM, ultrafine particles and transition metals increases cellular level of ROS [58,[79][80][81]. There are three potential sources of cellular ROS, which include NADPH oxidases, uncoupled nitric oxide synthase reaction or electron leak from the mitochondrial respiratory chain [82]. Obtained data clearly indicate that ROS produced by human monocyte exposed to PM are mainly of mitochondria origin. ...
According to the World Health Organization (WHO), air pollution is one of the most serious threats for our planet. Despite a growing public awareness of the harmful effects of air pollution on human health, the specific influence of particulate matter (PM) on human immune cells remains poorly understood. In this study, we investigated the effect of PM on peripheral blood monocytes in vitro. Monocytes from healthy donors (HD) were exposed to two types of PM: NIST (SRM 1648a, standard urban particulate matter from the US National Institute for Standards and Technology) and LAP (SRM 1648a with the organic fraction removed). The exposure to PM-induced mitochondrial ROS production followed by the decrease of mitochondrial membrane potential and activation of apoptotic protease activating factor 1 (Apaf-1), Caspase-9, and Caspase-3, leading to the cleavage of Gasdermin E (GSDME), and initiation of pyroptosis. Further analysis showed a simultaneous PM-dependent activation of inflammasomes, including NLRP3 (nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3) and Caspase-1, followed by cleavage of Gasdermin D (GSDMD) and secretion of IL-1β. These observations suggest that PM-treated monocytes die by pyroptosis activated by two parallel signaling pathways, related to the inorganic and organic PM components. The release of IL-1β and expression of danger-associated molecular patterns (DAMPs) by pyroptotic cells further activated the remnant viable monocytes to produce inflammatory cytokines (TNF-α, IL-6, IL-8) and protected them from death induced by the second challenge with PM.
In summary, our report shows that PM exposure significantly impacts monocyte function and induces their death by pyroptosis. Our observations indicate that the composition of PM plays a crucial role in this process—the inorganic fraction of PM is responsible for the induction of the Caspase-3-dependent pyroptotic pathway. At the same time, the canonical inflammasome path is activated by the organic components of PM, including LPS (Lipopolysaccharide/endotoxin).
Graphical Abstract
PM-induced pyroptosis of human monocytes. Particulate matter (PM) treatment affects monocytes viability already after 15 min of their exposure to NIST or LAP in vitro. The remnant viable monocytes in response to danger-associated molecular patterns (DAMPs) release pro-inflammatory cytokines and activate Th1 and Th17 cells. The mechanism of PM-induced cell death includes the increase of reactive oxygen species (ROS) production followed by collapse of mitochondrial membrane potential (ΔΨm), activation of Apaf-1, Caspase-9 and Caspase-3, leading to activation of Caspase-3-dependent pyroptotic pathway, where Caspase-3 cleaves Gasdermin E (GSDME) to produce a N-terminal fragment responsible for the switch from apoptosis to pyroptosis. At the same time, PM activates the canonical inflammasome pathway, where activated Caspase-1 cleaves the cytosolic Gasdermin D (GSDMD) to produce N-terminal domain allowing IL-1β secretion. As a result, PM-treated monocytes die by pyroptosis activated by two parallel pathways—Caspase-3-dependent pathway related to the inorganic fraction of PM and the canonical inflammasome pathway dependent on the organic components of PM.
... The imbalance between the production of free radicals and the function of the antioxidant system is defined as oxidative stress, whose role is discussed in the pathogenesis of some inflammatory and immune diseases such as AITDs [30,[42][43][44][45][46][47]. Environmental factors result in the excessive production of reactive oxygen species (ROS), leading to the modification of tissue proteins, the irregularity of the immune system, and the onset of autoimmune diseases (ADs); in addition, the aggravation of the pro-inflammatory state, tissue destruction, and the progression of ADs are other consequences of excessive production of ROS [48]. CRP is produced as an acute phase reactant in the liver and plays a role in response to inflammatory cytokines, including IL-6 [49]. ...
Background:
Primary hypothyroidism is a common endocrine disorder caused by impaired production of thyroid hormones. Recent studies have shown that dietary habits, oxidative stress, and inflammation may play roles in thyroid hypofunction. Thus, the present article aimed to determine the relationship between major dietary patterns and oxidative stress and inflammation in primary hypothyroid patients and healthy people in Iranian adults.
Methods:
This matched case-control study was conducted on 200 participants (100 cases and 100 controls). The presence of primary hypothyroidism was determined by endocrinologists based on American Thyroid Association (ATA) criteria. Dietary intake was assessed using a validated 168-item, semi-quantitative food frequency questionnaire (FFQ). The principal component analysis (PCA) method was used to derive major dietary patterns. Statistical analysis was performed using logistic regression analysis, and the findings were reported using odds ratios (ORs) with 95% CIs.
Results:
We identified 2 major dietary patterns (i.e., healthy and Western dietary patterns). After adjusting for confounding variables, participants in the highest tertile of the healthy eating pattern had lower odds of primary hypothyroidism. Also, there was a significant relationship between total antioxidant capacity (TAC) levels and thyroid hypofunction; however, no significant correlation was seen between the Western dietary pattern and malondialdehyde (MDA) and C-reactive protein (CRP) with hypothyroidism.
Conclusions:
There were statistically direct associations between healthy dietary patterns (loaded with vegetables, nuts and seeds, fruits, dried fruits, olives, garlic, black pepper, starchy vegetables, low-fat dairy, and legumes) and increased TAC levels with a decreased risk of thyroid hypofunction. However, Western dietary patterns and MDA and CRP levels did not associate with an underactive thyroid.
