Insights in the Role of Lipids, Oxidative Stress and Inflammation in Rheumatoid Arthritis Unveiled by New Trends in Lipidomic Investigations

Rheumatoid arthritis (RA) is a highly debilitating chronic inflammatory autoimmune disease most prevalent in women. The true etiology of this disease is complex, multifactorial, and is yet to be completely elucidated. However, oxidative stress and lipid peroxidation are associated with the development and pathogenesis of RA. In this case, oxidative damage biomarkers have been found to be significantly higher in RA patients, associated with the oxidation of biomolecules and the stimulation of inflammatory responses. Lipid peroxidation is one of the major consequences of oxidative stress, with the formation of deleterious lipid hydroperoxides and electrophilic reactive lipid species. Additionally, changes in the lipoprotein profile seem to be common in RA, contributing to cardiovascular diseases and a chronic inflammatory environment. Nevertheless, changes in the lipid profile at a molecular level in RA are still poorly understood. Therefore, the goal of this review was to gather all the information regarding lipid alterations in RA analyzed by mass spectrometry. Studies on the variation of lipid profile in RA using lipidomics showed that fatty acid and phospholipid metabolisms, especially in phosphatidylcholine and phosphatidylethanolamine, are affected in this disease. These promising results could lead to the discovery of new diagnostic lipid biomarkers for early diagnosis of RA and targets for personalized medicine.

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The Role of Src Kinase in Macrophage-Mediated Inflammatory Responses

Mediators of Inflammation ◽

10.1155/2012/512926 ◽

2012 ◽

Vol 2012 ◽

pp. 1-18 ◽

Cited By ~ 115

Author(s):

Se Eun Byeon ◽

Young-Su Yi ◽

Jueun Oh ◽

Byong Chul Yoo ◽

Sungyoul Hong ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Immune Responses ◽

Inflammatory Responses ◽

Inflammatory Diseases ◽

Src Kinase ◽

Multiple Roles ◽

Cellular Migration ◽

Pharmaceutical Drugs ◽

Tyrosine Protein Kinase

Src kinase (Src) is a tyrosine protein kinase that regulates cellular metabolism, survival, and proliferation. Many studies have shown that Src plays multiple roles in macrophage-mediated innate immunity, such as phagocytosis, the production of inflammatory cytokines/mediators, and the induction of cellular migration, which strongly implies that Src plays a pivotal role in the functional activation of macrophages. Macrophages are involved in a variety of immune responses and in inflammatory diseases including rheumatoid arthritis, atherosclerosis, diabetes, obesity, cancer, and osteoporosis. Previous studies have suggested roles for Src in macrophage-mediated inflammatory responses; however, recently, new functions for Src have been reported, implying that Src functions in macrophage-mediated inflammatory responses that have not been described. In this paper, we discuss recent studies regarding a number of these newly defined functions of Src in macrophage-mediated inflammatory responses. Moreover, we discuss the feasibility of Src as a target for the development of new pharmaceutical drugs to treat macrophage-mediated inflammatory diseases. We provide insights into recent reports regarding new functions for Src that are related to macrophage-related inflammatory responses and the development of novel Src inhibitors with strong immunosuppressive and anti-inflammatory properties, which could be applied to various macrophage-mediated inflammatory diseases.

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Critical Role of Zinc as Either an Antioxidant or a Prooxidant in Cellular Systems

Oxidative Medicine and Cellular Longevity ◽

10.1155/2018/9156285 ◽

2018 ◽

Vol 2018 ◽

pp. 1-11 ◽

Cited By ~ 48

Author(s):

Sung Ryul Lee

Keyword(s):

Oxidative Stress ◽

Zinc Deficiency ◽

Metal Binding ◽

Inflammatory Responses ◽

Binding Capacity ◽

Critical Role ◽

Cellular Systems ◽

Oxidative Stresses ◽

Dual Action

Zinc is recognized as an essential trace metal required for human health; its deficiency is strongly associated with neuronal and immune system defects. Although zinc is a redox-inert metal, it functions as an antioxidant through the catalytic action of copper/zinc-superoxide dismutase, stabilization of membrane structure, protection of the protein sulfhydryl groups, and upregulation of the expression of metallothionein, which possesses a metal-binding capacity and also exhibits antioxidant functions. In addition, zinc suppresses anti-inflammatory responses that would otherwise augment oxidative stress. The actions of zinc are not straightforward owing to its numerous roles in biological systems. It has been shown that zinc deficiency and zinc excess cause cellular oxidative stress. To gain insights into the dual action of zinc, as either an antioxidant or a prooxidant, and the conditions under which each role is performed, the oxidative stresses that occur in zinc deficiency and zinc overload in conjunction with the intracellular regulation of free zinc are summarized. Additionally, the regulatory role of zinc in mitochondrial homeostasis and its impact on oxidative stress are briefly addressed.

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Redox Status in Women with Rheumathoid Arthritis

Serbian Journal of Experimental and Clinical Research ◽

10.2478/sjecr-2018-0047 ◽

2018 ◽

Vol 0 (0) ◽

Cited By ~ 1

Author(s):

Aleksandra Vranic ◽

Aleksandra Antovic ◽

Nevena Draginic ◽

Marijana Andjic ◽

Marko Ravic ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Oxidative Stress ◽

Hydrogen Peroxide ◽

Lipid Peroxidation ◽

Superoxide Dismutase ◽

Cartilage Damage ◽

Thiobarbituric Acid ◽

Antioxidant Defense System ◽

Redox Status ◽

Female Population

Abstract The aim of this study was to assess oxidative status and to set baseline characteristics for female population with established rheumatoid arthritis. Total of 42 patients with rheumatoid arthritis and 48 age- and sex-matched controls were included in the study. Clinical examination was performed and assessed disease activity. Peripheral blood samples were used for all the assays. The markers of oxidative stress were assessed, including plasma levels of index of lipid peroxidation - thiobarbituric acid reactive substances, hydrogen peroxide, superoxide anion radical, nitrites and activity of superoxide dismutase, catalase and reduced glutathione levels as antioxidant parameters. In the patients group, levels of hydrogen peroxide and index of lipid peroxidation were higher than in controls. Patients with rheumatoid arthritis had decreased superoxide dismutase and catalase activity compared to healthy subjects. Interestingly, controls had higher levels of nitrites compared to patients. Patients showed a marked increase in reactive oxygen species formation and lipid peroxidation as well as decrease in the activity of antioxidant defense system leading to oxidative stress which may contribute to tissue and cartilage damage and hence to the chronicity of the disease.

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Introduction: Role of lipid peroxidation and oxidative stress in alcohol toxicity

Free Radical Biology and Medicine ◽

10.1016/0891-5849(89)90029-4 ◽

1989 ◽

Vol 7 (5) ◽

pp. 537-539 ◽

Cited By ~ 120

Author(s):

Arthur I. Cederbaum

Keyword(s):

Oxidative Stress ◽

Lipid Peroxidation ◽

And Oxidative Stress

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Curcumin and Endometriosis

International Journal of Molecular Sciences ◽

10.3390/ijms21072440 ◽

2020 ◽

Vol 21 (7) ◽

pp. 2440 ◽

Cited By ~ 1

Author(s):

Alexandre Vallée ◽

Yves Lecarpentier

Keyword(s):

Oxidative Stress ◽

Inflammatory Responses ◽

Uterine Cavity ◽

Main Role ◽

Oxygen Species ◽

Inflammatory Agent ◽

Gynecological Disorders ◽

Anti Oxidant ◽

Anti Inflammatory

Endometriosis is one of the main common gynecological disorders, which is characterized by the presence of glands and stroma outside the uterine cavity. Some findings have highlighted the main role of inflammation in endometriosis by acting on proliferation, apoptosis and angiogenesis. Oxidative stress, an imbalance between reactive oxygen species and antioxidants, could have a key role in the initiation and progression of endometriosis by resulting in inflammatory responses in the peritoneal cavity. Nevertheless, the mechanisms underlying this disease are still unclear and therapies are not currently efficient. Curcumin is a major anti-inflammatory agent. Several findings have highlighted the anti-oxidant, anti-inflammatory and anti-angiogenic properties of curcumin. The purpose of this review is to summarize the potential action of curcumin in endometriosis by acting on inflammation, oxidative stress, invasion and adhesion, apoptosis and angiogenesis.

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Guanxinshutong Alleviates Atherosclerosis by Suppressing Oxidative Stress and Proinflammation in ApoE−/− Mice

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/1219371 ◽

2020 ◽

Vol 2020 ◽

pp. 1-13

Author(s):

Yingdong Lu ◽

Yuchan Sun ◽

Zhilin Jiang ◽

Dandan Zhang ◽

Hongchen Lin ◽

...

Keyword(s):

Oxidative Stress ◽

Lipid Profile ◽

Inflammatory Responses ◽

Controlled Trial ◽

Immunohistochemical Analysis ◽

Computational Prediction ◽

Lipid Lowering ◽

Network Pharmacology ◽

Related Factors ◽

And Oxidative Stress

Atherosclerosis (AS) is a chronic progressive disease related to dyslipidemia, inflammation, and oxidative stress. Guanxinshutong capsule (GXST), a traditional Chinese medicine, has been widely used in treating coronary atherosclerotic heart disease, while its mechanism actions on AS are still not to be well addressed. Our present study is aimed to examine the effect of GXST on AS and elucidate the multitarget mechanisms of GXST on AS. Network pharmacology analysis was employed to screen the multitarget mechanisms of GXST on AS. ApoE−/− mice were used to validate these effects. Circulating lipid profile and oxidative stress-related factors were measured by the Elisa kit. Furthermore, the aortic trunk and aortic root were excised for oil red O staining, histopathological and immunohistochemical analysis. We first discovered that GXST was clued to exert synergistically antiatherosclerosis properties including lipid-lowering, anti-inflammation, and antioxidation through the computational prediction based on a network pharmacology simulation. Next, the validation experiments in atherosclerosis mice provided evidence that GXST significantly reduced atherosclerotic lesions, increased collagen deposition, and attenuated LV remodeling to some extent. Mechanistically, GXST modulated lipid profile, downregulated the level of inflammatory cytokines and NF-κBp65. GXST also reduced the activity of oxidative parameter MDA and upregulated the activities of antioxidant enzymes (SOD and GSH) compared with the AS model group. In conclusion, GXST intervention might attenuate atherosclerosis by mechanisms involving reducing lipid deposition, modulating oxidative stress and inflammatory responses, but a larger controlled trial is necessary for confirmation.

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Simvastatin Attenuates Contrast-Induced Nephropathy through Modulation of Oxidative Stress, Proinflammatory Myeloperoxidase, and Nitric Oxide

Oxidative Medicine and Cellular Longevity ◽

10.1155/2012/831748 ◽

2012 ◽

Vol 2012 ◽

pp. 1-8 ◽

Cited By ~ 24

Author(s):

Ketab E. Al-Otaibi ◽

Abdulrahman M. Al Elaiwi ◽

Mohammad Tariq ◽

Abdulrahman K. Al-Asmari

Keyword(s):

Oxidative Stress ◽

Nitric Oxide ◽

Femoral Vein ◽

Lipid Hydroperoxides ◽

Sprague Dawley ◽

Glycerol Injection ◽

Sprague Dawley Rats ◽

Structural Abnormalities ◽

Nephroprotective Effect

Contrast media- (CM-) induced nephropathy is a serious complication of radiodiagnostic procedures. Available data suggests that the development of prophylaxis strategies is limited by poor understanding of pathophysiology of CM-induced nephropathy. Present study was designed to determine the role of oxidative stress, myeloperoxidase, and nitric oxide in the pathogenesis of iohexol model of nephropathy and its modification with simvastatin (SSTN). Adult Sprague Dawley rats were divided into seven groups. After 24 h of water deprivation, all the rats except in control and SSTN-only groups were injected (10 ml/kg) with 25% glycerol. After 30 min, SSTN (15, 30, and 60 mg/kg) was administered orally, daily for 4 days. Twenty-four hours after the glycerol injection, iohexol was infused (8 ml/kg) through femoral vein over a period of 2 min. All the animals were sacrificed on day 5 and blood and kidneys were collected for biochemical and histological studies. The results showed that SSTN dose dependently attenuated CM-induced rise of creatinine, urea, and structural abnormalities suggesting its nephroprotective effect. A significant increase in oxidative stress (increased lipid hydroperoxides and reduced glutathione levels) and myeloperoxidase (MPO) and decreased nitric oxide in CM group were reversed by SSTN. These findings support the use of SSTN to combat CM-induced nephrotoxicity.

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