Vascular and cardiac oxidative stress and inflammation as targets for cardioprotection

2021 ◽  
Vol 27 ◽  
Author(s):  
Andreas Daiber ◽  
Sebastian Steven ◽  
Gerhild Euler ◽  
Rainer Schulz
Keyword(s):  
Oxidative Stress ◽  
Large Scale ◽  
Vascular Diseases ◽  
Cardiovascular Effects ◽  
Inflammatory Cells ◽  
Cellular Redox ◽  
Cardiac Inflammation ◽  
Inflammatory Processes ◽  
Anti Inflammatory ◽  
Shed Light

: Cardiac and vascular diseases are often associated with increased oxidative stress and inflammation, and both may contribute to the disease progression. However, successful applications of antioxidants in the clinical setting are very rare and specific anti-inflammatory therapeutics only emerged recently. Reasons for this rely on the great diversity of oxidative stress and inflammatory cells that can either act as cardioprotective or cause tissue damage in the heart. Recent large-scale clinical trials found that highly specific anti-inflammatory therapies using monoclonal antibodies against cytokines resulted in lower cardiovascular mortality in patients with pre-existing atherosclerotic disease. In addition, unspecific antiinflammatory medication and established cardiovascular drugs with pleiotropic immunomodulatory properties such as angiotensin converting enzyme (ACE) inhibitors or statins have proven beneficial cardiovascular effects. Normalization of oxidative stress seems to be a common feature of these therapies, which can be explained by a close interaction/crosstalk of the cellular redox state and inflammatory processes. In this review we give an overview about cardiac reactive oxygen species (ROS) sources and processes of cardiac inflammation, as well as the connection of ROS and inflammation, in ischemic cardiomyopathy in order to shed light on possible cardioprotective interventions.

scholarly journals Metformin and its anti-inflammatory and anti-oxidative effects; new concepts

2018 ◽  
Vol 8 (1) ◽  
pp. 54-61 ◽  
Author(s):  
Ali Hasanpour Dehkordi ◽  
Abolfazl Abbaszadeh ◽  
Samareh Mir ◽  
Amin Hasanvand
Keyword(s):  
Oxidative Stress ◽  
Cellular Level ◽  
Stress Factors ◽  
Inflammatory Factors ◽  
New Concepts ◽  
Appropriate Treatment ◽  
Inflammatory Processes ◽  
Anti Inflammatory ◽  
Oxidative Effects

Metformin is one of the oldest and commonly used blood sugar lowering drugs, having limited side effects and used as the first line treatment in patients suffering from diabetes mellitus. Moreover, various studies have emphasized on the anti-inflammatory and antioxidant role of metformin, with multiple mechanisms, which activation of AMPK by metformin has had a key role in many of them. During the searches on the internet websites of PubMed, Elsevier, Google Scholar, and Science Direct, 76 papers related to the anti-inflammatory and antioxidant role of metformin were selected and reviewed since 2003 to 2017. At the cellular level, metformin suppresses the inflammation in many cases and reduces or eliminates inflammatory factors mainly through dependent mechanisms and sometimes independent of AMPK at the cellular level and through other ways at the systematic levels. It is also effective in reducing the level of oxidative stress factors by regulating the antioxidant system of the cell. All evidence suggests the antioxidant and anti-inflammatory role of metformin in various conditions. Metformin can be an appropriate treatment option for many diseases, which inflammatory processes and oxidative stress play a role in their pathogenesis.

scholarly journals Characterization and validation of a chronic retinal neovascularization rabbit model by evaluating the efficacy of anti-angiogenic and anti-inflammatory drugs

2022 ◽  
Vol 15 (1) ◽  
pp. 15-22
Author(s):  
Sandeep Kumar ◽  
◽  
Nicholas Cook ◽  
Glenwood Gum ◽  
Vatsala Naageshwaran ◽  
...  
Keyword(s):  
Rabbit Model ◽  
Vascular Diseases ◽  
Inflammatory Cells ◽  
Retinal Hemorrhage ◽  
Vascular Leakage ◽  
Retinal Neovascularization ◽  
Fundus Photography ◽  
Duration Of Action ◽  
Before And After ◽  
Anti Inflammatory

AIM: To establish a rabbit model with chronic condition of retinal neovascularization (RNV) induced by intravitreal (IVT) injection of DL-2-aminoadipic acid (DL-AAA), a retinal glial (Müller) cell toxin, extensive characterization of DL-AAA induced angiographic features and the suitability of the model to evaluate anti-angiogenic and anti-inflammatory therapies for ocular vascular diseases. METHODS: DL-AAA (80 mmol/L) was administered IVT into both eyes of Dutch Belted rabbit. Post DL-AAA delivery, clinical ophthalmic examinations were performed weekly following modified McDonald-Shadduck Scoring System. Color fundus photography, fluorescein angiography (FA), and optical coherence tomography (OCT) procedures were performed every 2 or 4wk until stable retinal vascular leakage was observed. Once stable retinal leakage (12wk post DL-AAA administration) was established, anti-vascular endothelial growth factor (VEGF) (bevacizumab, ranibizumab and aflibercept) and anti-inflammatory (triamcinolone, TAA) drugs were tested for their efficacy after IVT administration. Fluorescein angiograms were scored before and after treatment following a novel grading system, developed for the DL-AAA rabbit model. RESULTS: Post DL-AAA administration, eyes were presented with moderate to severe retinal/choroidal inflammation which was accompanied by intense vitreous flare and presence of inflammatory cells in the vitreous humor. Retinal hemorrhage was restricted to the tips of neo-retinal vessels. FA revealed maximum retinal vascular leakage at 2wk after DL-AAA injection and then persisted as evidenced by stable mean FA scores in weeks 8 and 12. Retinal vascular angiographic and tomographic features were stable and consistent up to 36mo among two different staggers induced for RNV at two different occasions. Day 7, mean FA scores showed that 1 µg/eye of bevacizumab, ranibizumab, aflibercept and 2 µg/eye of TAA suppress 65%, 90%, 100% and 50% retinal vascular leakage, respectively. Day 30, bevacizumab and TAA continued to show 66% and 44% suppression while ranibizumab effect was becoming less effective (68%). In contrast, aflibercept was still able to fully (100%) suppress vascular leakage on day 30. On day 60, bevacizumab, ranibizumab and TAA showed suppression of 7%, 12%, and 9% retinal vascular leakage, respectively, however, aflibercept continued to be more effective showing 50% suppression of vascular leakage. CONCLUSION: The DL-AAA rabbit model mimics RNV angiographic features like RNV and chronic retinal leakage. Based on these features the DL-AAA rabbit model provides an invaluable tool that could be used to test the therapeutic efficacy and duration of action of novel anti-angiogenic formulations, alone or in combination with anti-inflammatory compounds.

scholarly journals GPRC5b Modulates Inflammatory Response in Glomerular Diseases via NF-κB Pathway

2019 ◽  
Vol 30 (9) ◽  
pp. 1573-1586 ◽  
Author(s):  
Sonia Zambrano ◽  
Katja Möller-Hackbarth ◽  
Xidan Li ◽  
Patricia Q. Rodriguez ◽  
Emmanuelle Charrin ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Knockout Mice ◽  
Large Scale ◽  
Molecular Mechanisms ◽  
Inflammatory Cells ◽  
Data Sets ◽  
Glomerular Diseases ◽  
Filtration Barrier ◽  
Inflammatory Processes

BackgroundInflammatory processes play an important role in the pathogenesis of glomerulopathies. Finding novel ways to suppress glomerular inflammation may offer a new way to stop disease progression. However, the molecular mechanisms that initiate and drive inflammation in the glomerulus are still poorly understood.MethodsWe performed large-scale gene expression profiling of glomerulus-associated G protein–coupled receptors (GPCRs) to identify new potential therapeutic targets for glomerulopathies. The expression of Gprc5b in disease was analyzed using quantitative PCR and immunofluorescence, and by analyzing published microarray data sets. In vivo studies were carried out in a podocyte-specific Gprc5b knockout mouse line. Mechanistic studies were performed in cultured human podocytes.ResultsWe identified an orphan GPCR, Gprc5b, as a novel gene highly enriched in podocytes that was significantly upregulated in common human glomerulopathies, including diabetic nephropathy, IgA nephropathy, and lupus nephritis. Similar upregulation of Gprc5b was detected in LPS-induced nephropathy in mice. Studies in podocyte-specific Gprc5b knockout mice showed that Gprc5b was not essential for normal development of the glomerular filtration barrier. However, knockout mice were partially protected from LPS-induced proteinuria and recruitment of inflammatory cells. Mechanistically, RNA sequencing in Gprc5b knockouts mice and experiments in cultured human podocytes showed that Gpr5cb regulated inflammatory response in podocytes via NF-κB signaling.ConclusionsGPRC5b is a novel podocyte-specific receptor that regulates inflammatory response in the glomerulus by modulating the NF-κB signaling pathway. Upregulation of Gprc5b in human glomerulopathies suggests that it may play a role in their pathogenesis.

scholarly journals Short-Term Nose-Only Water-Pipe (Shisha) Smoking Exposure Accelerates Coagulation and Causes Cardiac Inflammation and Oxidative Stress in Mice

2015 ◽  
Vol 35 (2) ◽  
pp. 829-840 ◽  
Author(s):  
Abderrahim Nemmar ◽  
Priya Yuvaraju ◽  
Sumaya Beegam ◽  
Badreldin H Ali
Keyword(s):  
Oxidative Stress ◽  
Platelet Aggregation ◽  
Plasma Concentrations ◽  
Cardiovascular Effects ◽  
Water Pipe ◽  
Short Term ◽  
Cardiac Inflammation ◽  
Short Term Exposure ◽  
And Oxidative Stress

Background/Aim: Water-pipe smoking (WPS) has acquired worldwide popularity, and is disseminating particularly rapidly in Europe and North America. However, little is known about the short-term cardiovascular effects of WPS. Methods: Presently, we assessed the short-term cardiovascular effects of nose-only exposure to mainstream WPS in BALB/c mice for 30 min/day for 5 consecutive days. Control mice were exposed to air. At the end of the exposure period, several cardiovascular endpoints were measured. Results: WPS did not affect the number of leukocytes and the plasma concentrations of C-reactive protein, tumor necrosis factor α (TNFα) and interleukin-6 (IL-6). Likewise, plasma levels of lipid peroxidation (LPO), reduced glutathione (GSH) and catalase were not affected by WPS. By contrast, WPS aggravated in vivo thrombosis by shortening the thrombotic occlusion time in pial arterioles and venules. The number of circulating platelets was reduced by WPS suggesting the occurrence of platelet aggregation in vivo. Elevated concentrations of fibrinogen and plasminogen activator inhibitor-1 were seen after the exposure to WPS. Blood samples taken from mice exposed to WPS and exposed to adenosine diphosphate showed more platelet aggregation. The heart concentrations of IL-6 and TNFα were augmented by WPS. Likewise, heart levels of LPO, reactive oxygen species and the antioxidants catalase and GSH were increased by WPS. However, the systolic blood pressure and heart rate were not affected by WPS. Conclusion: It can be concluded that short-term exposure to WPS exerts procoagulatory effects and induce cardiac inflammation and oxidative stress. At the time point investigated, there was no evidence for blood inflammation or oxidative stress.

scholarly journals Chemical Composition and Pharmacological Effects of Geopropolis Produced byMelipona quadrifasciata anthidioides

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Cintia Miranda dos Santos ◽  
Jaqueline Ferreira Campos ◽  
Helder Freitas dos Santos ◽  
José Benedito Perrella Balestieri ◽  
Denise Brentan Silva ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Chemical Composition ◽  
Antimicrobial Activities ◽  
Pharmacological Effects ◽  
Antimicrobial Drug Resistance ◽  
Gram Positive Bacteria ◽  
Microbial Infections ◽  
Inflammatory Processes ◽  
Anti Inflammatory ◽  
Hydroethanolic Extract

Stingless bees produce geopropolis, which is popularly described for its medicinal properties, but for which few scientific studies have demonstrated pharmacological effects. The objective of this study was to investigate the chemical composition of the geopropolis ofMelipona quadrifasciata anthidioidesand to evaluate its antioxidant, antimutagenic, anti-inflammatory, and antimicrobial activities. The composition of the hydroethanolic extract of geopropolis (HEG) included di- and trigalloyl and phenylpropanyl heteroside derivatives, flavanones, diterpenes, and triterpenes. HEG showed antioxidant action via the direct capture of free radicals and by inhibiting the levels of oxidative hemolysis and malondialdehyde in human erythrocytes under oxidative stress. HEG also reduced the frequency of gene conversion and the number of mutant colonies ofS. cerevisiae. The anti-inflammatory action of HEG was demonstrated by the inhibition of hyaluronidase enzyme activity. In addition, HEG induced cell death in all evaluated gram-positive bacteria, gram-negative bacteria, and yeasts, including clinical isolates with antimicrobial drug resistance. Collectively, these results demonstrate the potential ofM. q. anthidioidesgeopropolis for the prevention and treatment of various diseases related to oxidative stress, mutagenesis, inflammatory processes, and microbial infections.

scholarly journals PEA/Polydatin: Anti-Inflammatory and Antioxidant Approach to Counteract DNBS-Induced Colitis

Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 464
Author(s):  
Alessio Filippo Peritore ◽  
Ramona D’Amico ◽  
Marika Cordaro ◽  
Rosalba Siracusa ◽  
Roberta Fusco ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Clinical Signs ◽  
Neutrophil Infiltration ◽  
Sirtuin 1 ◽  
Positive Staining ◽  
Related Factor ◽  
Nuclear Factor ◽  
Protective Effects ◽  
Inflammatory Processes ◽  
Anti Inflammatory

Palmitoylethanolamide (PEA) has well-known anti-inflammatory effects. However, PEA does not possess an antioxidant ability. A comicronized formulation of ultramicronized PEA (um-PEA) and polydatin (Pol) PEA/Pol, a biological precursor of resveratrol with antioxidant activity, could have protective effects on oxidative stress produced by inflammatory processes. We evaluated the effects of a comicronized PEA/Pol 10 mg/kg (9 mg of um-PEA+1 mg of polydatin) in a model of Dinitrobenzene sulfonic acid (DNBS)-induced colitis. Ulcerative colitis was induced in mice by intrarectally injection of DNBS (4 mg in 100 µL of 50% ethanol per mouse). Macroscopic and histologic colon alterations and marked clinical signs were observed four days after DNBS and elevated cytokine production. The myeloperoxidase (MPO) activity assessed for neutrophil infiltration was associated with ICAM-1 and P-selectin adhesion controls in colons. Oxidative stress was detected with increased poly ADP-ribose polymerase (PARP) and nitrotyrosine positive staining and malondialdehyde (MDA) levels in inflamed colons. Macroscopic and histologic alterations minimized by oral PEA/Pol, as well as neutrophil infiltration, inflammatory cytokine release, MDA, nitrotyrosine, PARP and ICAM-1, and P-selectin expressions. The mechanism of action of PEA/Pol could be related to the sirtuin 1/nuclear factor erythroid 2-related factor 2 (SIRT-1/Nrf2) pathway and nuclear factor (NF)-κB. PEA/Pol administration inhibited NF-κB and increased SIRT-1/Nrf2 expressions. Our results show that PEA/Pol is capable of decreasing inflammatory bowel disease (IBD) DNBS-induced in mice.

Beneficial effect of Bidens pilosa L. (Asteraceae) in a rat model of colitis

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Oyindamola O. Abiodun ◽  
Aderemi S. Sosanya ◽  
Norah Nwadike ◽  
Adedunke O. Oshinloye
Keyword(s):  
Oxidative Stress ◽  
Wistar Rats ◽  
Intestinal Inflammation ◽  
Inflammatory Cells ◽  
Response To Treatment ◽  
Trinitrobenzene Sulfonic Acid ◽  
Bidens Pilosa ◽  
Treatment Groups ◽  
Beneficial Effects ◽  
Anti Inflammatory

AbstractBackgroundBidens pilosa (BP) possessed anti-inflammatory, antioxidant, and immunomodulatory activities. Its beneficial effects on intestinal inflammation and oxidative stress in 2,4,6 trinitrobenzene sulfonic acid (TNBS) induced colitis in Wistar rats was evaluated.MethodsThirty female Wistar rats weighing 180–200 g were distributed into six groups (n = 5): non-colitic, untreated colitic and colitic rats treated graded doses of methanol extract of BP (50–400 mg/kg). Colitis was induced in rats by intracolonic instillation of 0.2 mL of 40 mg/mL TNBS. BP was administered two days pre-colitis induction and treatments continued until seven days post-colitis induction. A day after the last treatment, rats were euthanized, colon removed aseptically and response to treatment assessed. Phytochemical composition of BP was determined using the GC-MS.ResultsBP significantly reduced macroscopic colonic damage score, weight/length ratio, colonic lipid peroxidation level, leukocytes infiltration, and TNF-α level in comparison to untreated colitic rats (p ≤ 0.008). Similarly, treatment with 200 and 400 mg/kg BP prevented depletion of colonic glutathione level than other treatment groups (p ≤ 0.0002). Histological findings revealed that treatment with 400 mg/kg BP significantly preserved the mucosal epithelial layer. It also prevented ulceration and sloughing of the mucosal layers and reduced infiltration of inflammatory cells compared to other treatment groups. Among the 16 compounds identified were oleic acid (6.2%) and n-hexadecanoic acid (2.0%) with antioxidant anti-inflammatory activities.ConclusionsThe beneficial effects of BP in rat colitis might be related to the reduction of leucocytes infiltration, inhibition of oxidative stress and pro-inflammatory cytokines.

scholarly journals An Overview on the Anti-inflammatory Potential and Antioxidant Profile of Eugenol

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Joice Nascimento Barboza ◽  
Carlos da Silva Maia Bezerra Filho ◽  
Renan Oliveira Silva ◽  
Jand Venes R. Medeiros ◽  
Damião Pergentino de Sousa
Keyword(s):  
Oxidative Stress ◽  
Therapeutic Potential ◽  
Inflammatory Diseases ◽  
Antioxidant Properties ◽  
Redox Status ◽  
Inhibitory Effect ◽  
New Drugs ◽  
Inflammatory Processes ◽  
Anti Inflammatory

The bioactive compounds found in foods and medicinal plants are attractive molecules for the development of new drugs with action against several diseases, such as those associated with inflammatory processes, which are commonly related to oxidative stress. Many of these compounds have an appreciable inhibitory effect on oxidative stress and inflammatory response, and may contribute in a preventive way to improve the quality of life through the use of a diet rich in these compounds. Eugenol is a natural compound that has several pharmacological activities, action on the redox status, and applications in the food and pharmaceutical industry. Considering the importance of this compound, the present review discusses its anti-inflammatory and antioxidant properties, demonstrating its mechanisms of action and therapeutic potential for the treatment of inflammatory diseases.

scholarly journals Oxidative stress and inflammation caused by n-Hexyl salicylate in mouse skin: the effectiveness of flavonoids

2017 ◽  
Vol 9 (2) ◽  
Author(s):  
Nada Orsolic ◽  
Vedran Balta ◽  
Dyana Odeh ◽  
Maja Mataković ◽  
Jadranka Skurić
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Peritoneal Cavity ◽  
Mouse Skin ◽  
Inflammatory Cells ◽  
Skin Lesions ◽  
Protective Role ◽  
Chronic Inflammatory Disease ◽  
Anti Inflammatory ◽  
Multifunctional Molecules

<p>Reactive oxygen species (ROS) play a role in a numbered of degenerative conditions including psoriasis. Psoriasis is a chronic inflammatory disease who’s the etiopathogenesis is not yet completely understood, and therefore there is no standardized therapeutical approach. Flavonoids, recognized as potent antioxidants, are multifunctional molecules that can act as anti-inflammatory and antiproliferative agents through the modulation of multiple signaling pathways. The present study was designed to investigate the protective role of flavonoids [quercetin, chrysin, curcumin or Epigallocatechin 3-gallate (EGCG)] against n-Hexyl salicylate (HXS)-induced oxidative stress and inflammation in skin. Anti-oxidative and anti-inflammatory effect of flavonoids is quantified by histopathological assessment of skin, measuring the levels of lipid peroxidation and glutathione (GSH) in the skin, total number of inflammatory cells in peritoneal cavity, macrophage spreading index, and hematological and biochemical parameters.</p><p>Topically applied of n-Hexyl salicylate caused significant increase in lipid peroxidation and decrease in GSH, which is accompanied by an increase<strong> </strong><em>total number of inflammatory cells in skin and peritoneal cavity, functional activity of macrophages, and enzymatic activity of ALP and AST.</em> In contrast, topically applied 5 % preparation of flavonoids (quercetin, chrysin, curcumin or EGCG) with HXS effectively prevented these alterations and maintained the antioxidant status.</p><p>The results suggest that flavonoid preparations can serve as a potent antioxidant and anti-inflammatory agents in psoriatic-like skin lesions, without toxic effects.</p>

scholarly journals Molecular Mechanism of the Anti-Inflammatory Action of Heparin

2021 ◽  
Vol 22 (19) ◽  
pp. 10730
Author(s):  
Leandar Litov ◽  
Peicho Petkov ◽  
Miroslav Rangelov ◽  
Nevena Ilieva ◽  
Elena Lilkova ◽  
...  
Keyword(s):  
Molecular Mechanism ◽  
Low Molecular Weight ◽  
Heparin Binding ◽  
High Affinity ◽  
Inflammatory Agent ◽  
Inflammatory Processes ◽  
Anti Inflammatory ◽  
Dynamics Simulations ◽  
Shed Light ◽  
Inflammatory Action

Our objective is to reveal the molecular mechanism of the anti-inflammatory action of low-molecular-weight heparin (LMWH) based on its influence on the activity of two key cytokines, IFNγ and IL-6. The mechanism of heparin binding to IFNγ and IL-6 and the resulting inhibition of their activity were studied by means of extensive molecular-dynamics simulations. The effect of LMWH on IFNγ signalling inside stimulated WISH cells was investigated by measuring its antiproliferative activity and the translocation of phosphorylated STAT1 in the nucleus. We found that LMWH binds with high affinity to IFNγ and is able to fully inhibit the interaction with its cellular receptor. It also influences the biological activity of IL-6 by binding to either IL-6 or IL-6/IL-6Rα, thus preventing the formation of the IL-6/IL-6Rα/gp130 signalling complex. These findings shed light on the molecular mechanism of the anti-inflammatory action of LMWH and underpin its ability to influence favourably conditions characterised by overexpression of these two cytokines. Such conditions are not only associated with autoimmune diseases, but also with inflammatory processes, in particular with COVID-19. Our results put forward heparin as a promising means for the prevention and suppression of severe CRS and encourage further investigations on its applicability as an anti-inflammatory agent.

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